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Increased use of antiviral monoclonal antibodies (mAbs) for treatment and prophylaxis necessitates better understanding of their impact on endogenous immunity to vaccines and viruses. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic presented an opportunity to study immunity in individuals who received antiviral mAbs and were subsequently immunized with vaccines encoding the mAb-targeted viral spike antigen. Here, we describe the impact of administration of an antibody combination, casirivimab plus imdevimab (CAS+IMD), on immune responses to subsequent SARS-CoV-2 vaccination in humans, nonhuman primates, and mice. The presence of CAS+IMD at the time of vaccination led to a specific diminishment of vaccine-elicited pseudovirus neutralizing antibody titers without overall dampening of spike protein–directed immune responses, including antibody, B cell, and T cell responses. The impact on pseudovirus neutralizing titers extended to other therapeutic anti–spike protein antibodies when used as either monotherapy or combination therapy. The specific reduction in pseudovirus neutralizing titers was the result of epitope masking, a phenomenon where specific epitopes are bound by high-affinity antibodies and blocked from B cell recognition. Encouragingly, this reduction in pseudovirus neutralizing titers was reversible with additional booster vaccination. Moreover, by assessing the antiviral immune response in SARS-CoV-2–infected individuals treated therapeutically with CAS+IMD, we demonstrated alteration of antiviral humoral immunity in those who had received mAb therapy, but only in those individuals who had yet to start mounting their natural immune response at the time of mAb treatment. Together, these data demonstrate that antiviral mAbs can alter endogenous humoral immunity during vaccination or infection. Editor's summary: Monoclonal antibody (mAb) therapies and vaccines were both essential tools for curbing the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. As vaccines were rolled out during clinical trials for mAb therapies, it offered Petro et al. a unique opportunity to ask how SARS-CoV-2 mAb therapy influenced vaccine responses. The authors found that mAb therapy with casirivimab plus imdevimab, given at the time of vaccination, altered vaccine-elicited immunity in humans, resulting in lower neutralizing titers; this observation was mirrored in data from both nonhuman primates and mice. Encouragingly, booster vaccinations restored neutralizing antibody titers. A similar study in humans who received casirivimab plus imdevimab during SARS-CoV-2 infection revealed that early mAb treatment also impaired elicitation of endogenous immunity. Together, these data shed light on the complex interplay among mAb therapies, vaccines, and infections. —Courtney Malo [ABSTRACT FROM AUTHOR]

Background: Coronavirus-2019 (COVID-19) vaccination in Australia commenced in February 2021. The first vaccines recommended for use were AZD1222 and BNT162b2, both delivered as a two-dose primary schedule. In the absence of sustained immunity following immunisation, recommendations for booster vaccination have followed. It is likely that periodic boosting will be necessary for at least some Australians, but it is unknown what the optimal booster vaccines and schedules are or for whom vaccination should be recommended. Methods: The Platform Trial In COVID-19 priming and BOOsting (PICOBOO) is a multi-site, multi-arm, randomised, Bayesian adaptive platform trial evaluating different booster vaccine interventions in immunocompetent children and adults, stratified by their primary vaccination schedule and age. Participants are randomised to receive one of three licensed COVID-19 booster vaccines available for use in Australia. PICOBOO aims to generate evidence about the immunogenicity, reactogenicity, and cross-protection of different booster vaccine strategies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants/subvariants. The protocol structure specifying PICOBOO is modular and hierarchical. We have previously published the PICOBOO core (master) protocol. Here, we detail the substudy protocol which outlines the study processes which are specific to PICOBOO participants enrolled in the booster vaccination substudy. Discussion: PICOBOO is an adaptive platform trial evaluating different COVID-19 booster vaccination strategies to generate evidence to inform immunisation practice and policy. The modular and flexible protocol structure is intended to enable investigators to respond with agility to new research questions as they arise, such as immunogenicity targeting emergent virus variants, and the immunogenicity and reactogenicity of new vaccines as they become available for use. Trial registration: Australian and New Zealand Clinical Trials Register ACTRN12622000238774; registered on 10/02/2022. Protocol V8.0_23112023. [ABSTRACT FROM AUTHOR]

Lung transplant recipients (LTRs) are susceptible to severe Coronavirus Disease 2019 (COVID-19) and had lower immune responses to primary severe acute respiratory syndrome-related to coronavirus 2 (SARS-CoV-2) vaccination as compared to the general population and to other solid organ transplant recipients. As immunity induced by booster vaccination and natural infection has increased since the beginning of the pandemic in the general population, immunity acquired by LTRs is not well documented. Humoral and cellular immunity to SARS-CoV-2 was monitored in February and May 2023 in 30 LTRs and compared to that of health care workers (HCWs) and nursing home residents (NHRs). LTRs had significantly lower levels of SARS-CoV-2 binding and neutralizing antibodies and lower interferon-gamma responses to Wuhan, Delta, and XBB1.5 variants as compared to HCWs and NHRs. Humoral immunity decreased between the 2 visits, whereas cellular immunity remained more stable. The persistent defect in SARS-CoV-2 immunity in LTRs should encourage continued monitoring and preventive measures for this vulnerable population. [ABSTRACT FROM AUTHOR]

Introduction: The United States Advisory Committee on Immunization Practices (ACIP) and the Centers for Disease Control (CDC) recommend COVID-19 vaccines for all immunocompromised individuals. Certain disease groups are at increased risk of comorbidity and death for which disease-specific recommendations should be considered. The objective of the Delphi panel of experts was to summarize expert consensus on COVID-19 vaccinations for patients with rheumatologic disease, renal disease, hematologic malignancy and solid organ transplant (SOT) in the US. Methods: A two-stage Delphi panel method was employed, starting with qualitative interviews with key opinion leaders (KOLs) in the four disease areas (n = 4 KOLs, n = 16 total) followed by three rounds of iterative revision of disease-specific COVID-19 vaccine recommendations. Final consensus was rated after the third round. Statements addressed primary and booster dosing (e.g., number and frequency) and other considerations such as vaccine type or heterologous messenger ribonucleic acid (mRNA) vaccination. Following the Delphi Panel, an online survey was conducted to assess physician agreement within the disease areas (n = 50 each, n = 200 total) with the consensus statements. Results: Moderate to strong consensus was achieved for all primary series vaccination statements across disease groups, except one in hematology. Similarly, moderate to strong consensus was achieved for all booster series statements in all disease areas. However, statements on antibody titer measurements for re-vaccination considerations and higher dosages for immunocompromised patients did not reach agreement. Overall, approximately 62%–96% of physicians strongly agreed with the primary and booster vaccine recommendations. However, low agreement (29%–69%) was found among physicians for time interval between disease-specific treatment and vaccination, recommendations for mRNA vaccines, heterologous mRNA vaccination, antibody titer measurement and higher vaccine dosage for immunocompromised groups. Conclusion: Consensus was achieved for disease-specific COVID-19 vaccine recommendations concerning primary and booster series vaccines and was generally well accepted by practicing physicians. [ABSTRACT FROM AUTHOR]

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare systems globally. The lack of quality guidelines on the management of COVID-19 in rheumatologic disease, renal disease, hematological malignancy, and solid organ transplant recipients has resulted in a wide variation in clinical practice. Methods: Using a Delphi process, a panel of 16 key opinion leaders developed clinical practice statements regarding vaccine recommendations in areas where standards are absent or limited. Agreement among practicing physicians with consensus statements was also assessed via an online physician survey. The strength of the consensus was determined by the following rating system: a strong rating was defined as all four key opinion leaders (KOLs) rating the statement ≥ 8, a moderate rating was defined as three out of four KOLs rating the statement ≥ 8, and no consensus was defined as less than three out of four KOLs provided a rating of ≤ 8. Specialists voted on agreement with each consensus statement for their disease area using the same ten-point scoring system. Results: Key opinion leaders in rheumatology, nephrology, and hematology achieved consensuses for all nine statements pertaining to the primary and booster series with transplant physicians reaching consensus on eight of nine statements. Experts agreed that COVID-19 vaccines are safe, effective, and well tolerated by patients with rheumatological conditions, renal disease, hematologic malignancy, and recipients of solid organ transplants. The Delphi process yielded strong to moderate suggestions for the use of COVID-19 messenger ribonucleic acid (mRNA) vaccines and the necessity of the COVID-19 booster for the immunocompromised population. The expert panel had mixed feelings concerning the measurement of antibody titers, higher-dose mRNA vaccines, and the development of disease-specific COVID-19 guidance. Conclusions: These results confirmed the necessity of COVID-19 vaccines and boosters in immunocompromised patients with rheumatologic disease, renal disease, hematological malignancy, and solid organ transplant recipients. Statements where consensus was not achieved were due to absent or limited evidence. [ABSTRACT FROM AUTHOR]

Incidence rates of Lyme borreliosis, a tickborne disease attributed to infection by Borrelia species, are increasing, and limitations to existing treatments potentiate the possibility of severe outcomes. Nevertheless, there are no licensed vaccines for Lyme borreliosis prevention in humans. This study investigated the immunogenicity and safety of a booster dose of VLA15, an investigational outer surface protein A (OspA)-based Lyme borreliosis vaccine that has previously shown safety and immunogenicity when administered as a primary vaccination series, following a primary VLA15 vaccination series. We report the results of the booster phase of a randomised, observer-blinded, placebo-controlled, multicentre, phase 2 study that enrolled healthy adults aged 18–65 years from five US clinical study centres to receive 135 μg or 180 μg VLA15 or placebo at months 0, 2, and 6 in the main study phase. Participants who received 180 μg VLA15 in the main study phase and did not have relevant protocol deviations were eligible for the booster phase (months 18–30). Participants were randomly reassigned (2:1) to receive an intramuscular injection of a VLA15 booster or placebo 1 year after the completion of primary vaccination (month 18) via a randomisation list generated by an unmasked statistician with a block size of six. Individuals involved in data safety monitoring, rerandomisation, vaccine handling, and vaccine accountability were unmasked; the study sponsor and statisticians were only unmasked after analysis of data up to 1 month after booster administration. All other individuals remained masked throughout the booster phase. The outcomes for the booster phase were the immunogenicity (evaluated in the booster per-protocol population) and safety (evaluated for all participants who received the booster) of the booster dose up to month 30. The study is registered at ClinicalTrials.gov (NCT03970733) and is completed. Between Feb 4 and March 23, 2021, 58 participants (28 men and 30 women) were screened, randomly assigned, and received VLA15 (n=39) or placebo (n=19). One participant in the placebo group was lost to follow-up. The IgG geometric mean titres for each OspA serotype (serotypes 1–6) in the VLA15 group peaked at 1 month after the booster dose (1277·0 U/mL [95% CI 861·8–1892·3] to 2194·5 U/mL [1566·8–3073·7] vs 23·6 U/mL [18·1–30·8] to 36·8 U/mL [26·4–51·3] in the placebo group [p<0·0001 for all serotypes]), remained elevated at month 24 (137·4 U/mL [95·8–196·9] to 265·8 U/mL [202·9–348·2] vs 22·3 U/mL [17·7–28·0] to 29·1 U/mL [20·8–40·6] in the placebo group; p<0·0001 for all serotypes), and declined by month 30 (54·1 U/mL [38·6–75·7] to 101·6 U/mL [77·6–133·1] vs 21·9 U/mL [18·0–26·6] to 24·9 U/mL [19·0–32·6] in the placebo group; p<0·0001 for all serotypes except serotype 1 [p=0·0006]). Solicited local adverse events were reported more frequently in the VLA15 group (35 [92%, 95% CI 79–97] of 38 participants) than the placebo group (six [32%, 15–54] of 19 participants; p<0·0001) after booster vaccination. There was no significant difference in the frequency of solicited systemic adverse events between groups (20 [59%, 42–74] of 34 participants in the VLA15 group vs six [38%, 18–61] of 16 participants in the placebo group). Related unsolicited adverse events (none severe) were reported by two (5%, 1–17) of 39 participants in the VLA15 group and none (0%, 0–17) of 19 participants in the placebo group. There were no severe solicited local or systemic adverse events or deaths during the study. A booster dose of VLA15 is safe and induces substantial anamnestic immune responses against all six OspA serotypes. As with previously investigated OspA-based Lyme borreliosis vaccines, waning immune responses were observed with VLA15, and annual boosters might therefore be required. Valneva. [ABSTRACT FROM AUTHOR]

Longitudinal analysis of antibody responses following three-dose COVID-19 vaccination in patients with chronic liver disease (CLD) has been limited. From August 2021 to February 2023, sequential anti -SARS-CoV-2 spike IgG titers were determined in 45 patients with CLD who received two or three doses of COVID-19 vaccine. The geometric mean of anti-spike IgG at four weeks after the second and third doses were 1313.16 BAU/mL and 3042.29 BAU/mL, respectively, and it decreased significantly from four to 24 weeks after the second (1313.16 vs. 198.42 BAU/mL, p = 0.002) and the third (3042.29 vs. 636.71 BAU/mL, p < 0.001) dose. The anti-spike IgG titers in participants receiving prime-boost homologous mRNA vaccines (BNT162b2 or mRNA-1273) were comparable between participants with and those without significant liver fibrosis at each follow-up time point. This study demonstrated a notable decrease in anti-spike IgG after completion of the vaccination schedule in patients with CLD, highlighting the importance of additional booster doses. [ABSTRACT FROM AUTHOR]

Background: Netherton syndrome (NS) is a rare, severe genetic skin disorder, currently classified as an inborn error of immunity (IEI) due to previously reported immune dysregulation. We recently reported the results of an immunological evaluation showing no evidence for a relevant B- and/or T-cell mediated immunodeficiency, but immune responses after vaccination were not evaluated in that study. Therefore, we evaluated immune responses to three vaccine platforms in adult NS patients to further investigate the presence of a clinically relevant B- and/or T-cell immunodeficiency. Methods: Vaccination responses in eight adult NS patients were assessed in a cross-sectional study performed between January and August 2022. Clinical patient data were retrospectively retrieved from electronic patient files. Immune responses to a polysaccharide Streptococcus pneumoniae vaccine (PPV23) and conjugate Haemophilus influenzae type b vaccine (ActHiB) were measured. SARS-CoV-2-specific (functional) antibody and T-cell responses following booster vaccination with an mRNA-based COVID-19 vaccine were compared to controls. Results: None of the included patients suffered from recurrent and/or severe infections that could be attributed to a B- and/or T-cell immunodeficiency. ActHiB induced immune responses were normal in 7/7 NS patients. PPV23 induced responses were absent in 1/7, diminished in 2/7, and normal in 4/7 patients. Levels of SARS-CoV-2-specific binding and neutralizing antibodies after mRNA-based COVID-19 booster vaccination in NS patients were comparable to controls. SARS-CoV-2-specific CD4 + T-cell responses were detectable in all NS patients. In contrast, SARS-CoV-2-specific CD8 + T-cell responses were detectable in only 2/6 NS patients. T-cell responses to a positive control antigen pool were comparable to controls. Conclusions: Vaccine-induced immune responses were detectable after polysaccharide, conjugate and mRNA-based vaccination in our cohort of NS patients. A spectrum of responsiveness to vaccine challenges was found, with the ranges of vaccine responses overlapping those demonstrated in healthy control populations. [ABSTRACT FROM AUTHOR]

Introduction: Acute myeloid leukemia (AML) has a dismal prognosis, mostly due to minimal residual disease-driven relapse, making an elimination of persisting therapy-resistant leukemia progenitor/stem cells (LPCs) the main goal for novel therapies. Peptide-based immunotherapy offers a low-side-effect approach aiming to induce T cell responses directed against human leukocyte antigen (HLA) presented tumor antigens on malignant cells by therapeutic vaccination. Mass spectrometry-based analysis of the naturally presented immunopeptidome of primary enriched LPC and AML samples enabled the selection of antigens exclusively expressed on LPC/AML cells, which showed de novo induction and spontaneous memory T cell responses in AML patients, and whose presentation and memory T cell recognition was associated with improved disease outcome. Methods: Based on these data the therapeutic vaccine AML-VAC-XS15 was designed, comprising two mutated HLA class I-restricted peptides from the common AML-specific mutation in NPM1 and seven HLA class II-restricted peptides (six non-mutated high-frequent AML/LPC-associated antigens and one mutated peptide from the AML-specific mutation R140Q in IDH2), adjuvanted with the toll like receptor 1/2 ligand XS15 and emulsified in Montanide ISA 51 VG. A phase I open label clinical trial investigating AML-VACX-S15 was designed, recruiting AML patients in complete cytological remission (CR) or CR with incomplete blood count recovery. Patients are vaccinated twice with a six-week interval, with an optional booster vaccination four months after 2nd vaccination, and are then followed up for two years. The trial's primary objectives are the assessment of the vaccine's immunogenicity, safety and toxicity, secondary objectives include characterization of vaccine-induced T cell responses and assessment of preliminary clinical efficacy. Ethics and dissemination: The AML-VAC-XS15-01 study was approved by the Ethics Committee of the Bavarian State medical association and the Paul-Ehrlich Institut (P01392). Clinical trial results will be published in peer-reviewed journals. [ABSTRACT FROM AUTHOR]

Hematological malignancies are associated with an increased risk of complications during SARS-CoV-2 infections. Primary series or monovalent booster vaccines reduce disease severity, hospitalization, and death among multiple myeloma patients. We characterized virus-neutralizing and spike-binding antibody profiles following monovalent (WA1) or bivalent (WA1/BA.5) SARS-CoV-2 booster vaccination in MM patients. Bivalent vaccination improved the breadth of binding antibodies but not neutralization activity against contemporary variants. Hybrid immunity and immune imprinting impact vaccine-elicited immunity. [ABSTRACT FROM AUTHOR]

RTS,S/AS01E, the first approved malaria vaccine, demonstrated moderate efficacy during the phase 3 pediatric trial. We previously investigated cell-mediated immune (CMI) responses following the primary 3-dose immunization and now report responses to the booster dose given 18 months later. Thirty CMI markers were measured by Luminex in supernatants of peripheral blood mononuclear cells from 709 children and infants after RTS,S/AS01E antigen stimulation, and their associations with malaria risk and antibodies one month post-booster and one year later were assessed. IL-2, IFN-γ, IL-17, IL-5, and IL-13 were associated with RTS,S/AS01E booster vaccination, and IL-2 responses to the circumsporozoite protein (CSP) remained higher after one year. IL-2 was associated with reduced malaria risk in one site, and IL-10 was associated with increased risk in infants. Anti-CSP IgG and IL-2 were moderately correlated one year after booster. This study highlights the moderate cell-mediated immunogenicity of the RTS,S/AS01E booster dose that aligns with partial recovery of RTS,S/AS01E vaccine efficacy. [ABSTRACT FROM AUTHOR]

Lipschütz ulcer (LU) is a condition known for painful vulvar ulcers, typically affecting young women and often linked to infectious agents. Recent reports have indicated a potential connection between LU and COVID‐19 vaccination, particularly after the second or booster doses. This study presents a case of LU following the first dose of tozinameran in a young woman who had a previous SARS‐CoV‐2 infection and investigates similar cases globally. An 18‐year‐old woman experienced vulvar pain and ulcers 2‐days after her initial COVID‐19 vaccine dose. After ruling out infections through serological tests, a diagnosis of LU was made, and her symptoms resolved after 10 days. A literature search and VigiBase® analysis revealed 11 cases of LU following COVID‐19 vaccination, and 519 vulvovaginal ulcer cases associated with these vaccines were identified in Vigibase®, with a median onset of 2 days. Most LU cases occurred after the second dose or booster shots. The primary hypothesis for this association is a type 3 hypersensitivity reaction mediated by immune complexes, possibly triggered by prior exposure, as many cases occurred after the second dose. Interestingly, the presented case suggests that prior COVID‐19 infection could serve as sensitization. In conclusion, this study highlights the potential occurrence of LU after the initial COVID‐19 vaccine dose in young patients with prior COVID‐19 infection. While the risk of recurrence after subsequent vaccinations or infections remains uncertain, the benefits of vaccination outweigh the risks. Clinicians and patients should be aware of this potential issue to make informed decisions regarding vaccination. [ABSTRACT FROM AUTHOR]

The systematic review compared the neutralizing antibody responses of CoronaVac and BNT162b2 vaccines in various populations. Studies showed that BNT162b2 generally elicited stronger immune responses than CoronaVac, especially against variants like Omicron and Delta. Heterologous vaccination strategies were found to result in more robust immune responses compared to homologous strategies, particularly in individuals with comorbidities or previous COVID-19 infections. Despite enhanced immune responses, the Omicron variant demonstrated the ability to evade neutralizing antibodies, even in individuals who received multiple doses of either vaccine. [Extracted from the article]

Current COVID-19 vaccines induce suboptimal respiratory mucosal immunity even after mRNA boosters (Declercq et al. and Lasrado et al., this issue). [ABSTRACT FROM AUTHOR]

Current COVID-19 vaccines provide robust protection against severe disease but minimal protection against acquisition of infection. Intramuscularly administered COVID-19 vaccines induce robust serum neutralizing antibodies (NAbs), but their ability to boost mucosal immune responses remains to be determined. In this study, we show that the XBB.1.5 messenger RNA (mRNA) boosters result in increased serum neutralization to multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in humans, including the dominant circulating variant JN.1. In contrast, we found that the XBB.1.5 mRNA booster did not augment mucosal NAbs or mucosal IgA responses, although acute SARS-CoV-2 XBB infection substantially increased mucosal antibody responses. These data demonstrate that current XBB.1.5 mRNA boosters substantially enhance peripheral antibody responses but do not robustly increase mucosal antibody responses. Our data highlight a separation between the peripheral and mucosal immune systems in humans and emphasize the importance of developing next-generation vaccines to augment mucosal immunity to protect against respiratory virus infections. Editor's summary: mRNA vaccines for SARS-CoV-2 elicit robust antibody responses in the circulation, which aid in protection from severe disease. However, the extent to which mRNA vaccines, which are delivered intramuscularly, can elicit mucosal immune responses is unclear. In a pair of papers, Declercq et al. and Lasrado et al. come to distinct conclusions. Using human nasal swab samples in both studies, Declercq et al. show that repeated vaccination for SARS-CoV-2 promotes neutralizing antibodies in the nose, whereas Lasrado et al. observed no obvious increase in neutralizing antibody titers after booster vaccination. These differing results may be due to the number of SARS-CoV-2 vaccinations or exposures, time since last exposure, and experimental approaches, but this pair of papers underscores the need to better understand the mucosal immune response in humans. —Courtney Malo [ABSTRACT FROM AUTHOR]

To prevent infection by respiratory viruses and consequently limit virus circulation, vaccines need to promote mucosal immunity. The extent to which the currently used messenger RNA (mRNA)–based COVID-19 vaccines induce mucosal immunity remains poorly characterized. We evaluated mucosal neutralizing antibody responses in a cohort of 183 individuals. Participants were sampled at several time points after primary adenovirus vector–based or mRNA-based COVID-19 vaccination and after mRNA-based booster vaccinations. Our findings revealed that repeated vaccination with mRNA boosters promoted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibodies in nasal secretions. Nasal and serum neutralizing antibody titers of both IgG and IgA isotypes correlated to one another. We investigated the source of these mucosal antibodies in a mouse model wherein mice received repeated mRNA vaccines for SARS-CoV-2. These experiments indicated that neutralizing antibody–producing cells reside in the spleen and bone marrow, whereas no proof of tissue homing to the respiratory mucosa was observed, despite the detection of mucosal antibodies. Serum transfer experiments confirmed that circulating antibodies were able to migrate to the respiratory mucosa. Collectively, these results demonstrate that, especially upon repeated vaccination, the currently used COVID-19 mRNA vaccines can elicit mucosal neutralizing antibodies and that vaccination might also stimulate mucosal immunity induced by previous SARS-CoV-2 infection. Moreover, migration of circulating antibodies to the respiratory mucosa might be a main mechanism. These findings advance our understanding of mRNA vaccine–induced immunity and have implications for the design of vaccine strategies to combat respiratory infections. Editor's summary: mRNA vaccines for SARS-CoV-2 elicit robust antibody responses in the circulation, which aid in protection from severe disease. However, the extent to which mRNA vaccines, which are delivered intramuscularly, can elicit mucosal immune responses is unclear. In a pair of papers, Declercq et al. and Lasrado et al. come to distinct conclusions. Using human nasal swab samples in both studies, Declercq et al. show that repeated vaccination for SARS-CoV-2 promotes neutralizing antibodies in the nose, whereas Lasrado et al. observed no obvious increase in neutralizing antibody titers after booster vaccination. These differing results may be due to the number of SARS-CoV-2 vaccinations or exposures, time since last exposure, and experimental approaches, but this pair of papers underscores the need to better understand the mucosal immune response in humans. —Courtney Malo [ABSTRACT FROM AUTHOR]

The outbreaks of severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2 highlight the need for countermeasures to prevent future coronavirus pandemics. Given the unpredictable nature of spillover events, preparing antibodies with broad coronavirus-neutralizing activity is an ideal proactive strategy. Here, we investigated whether SARS-CoV-2 infection and vaccination could provide cross-neutralizing antibodies (nAbs) against zoonotic sarbecoviruses. We evaluated the cross-neutralizing profiles of plasma and monoclonal antibodies constructed from B cells from coronavirus disease 2019 (COVID-19) convalescents and vaccine recipients; against sarbecoviruses originating from bats, civets, and pangolins; and against SARS-CoV-1 and SARS-CoV-2. We found that the majority of individuals with natural infection and vaccination elicited broad nAb responses to most tested sarbecoviruses, particularly to clade 1b viruses, but exhibited very low cross-neutralization to SARS-CoV-1 in both natural infection and vaccination, and vaccination boosters significantly augmented the magnitude and breadth of nAbs to sarbecoviruses. Of the nAbs, several exhibited neutralization activity against multiple sarbecoviruses by targeting the spike receptor-binding domain (RBD) and competing with angiotensin-converting enzyme 2 (ACE2) binding. SCM12-61 demonstrated exceptional potency, with half-maximal inhibitory concentration (IC50) values of 0.001–0.091 μg/mL against tested sarbecoviruses; while VSM9-12 exhibited remarkable cross-neutralizing breadth against sarbecoviruses and SARS-CoV-2 Omicron subvariants, highlighting the potential of these two nAbs in combating sarbecoviruses and SARS-CoV-2 Omicron subvariants. Collectively, our findings suggest that vaccination with an ancestral SARS-CoV-2 vaccine, in combination with broad nAbs against sarbecoviruses, may provide a countermeasure for preventing further sarbecovirus outbreaks in humans. [ABSTRACT FROM AUTHOR]

Introduction: Solid organ transplant (SOT) recipients display weak seroconversion and neutralizing antibody (NAb) responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and remain at risk of severe coronavirus disease 2019 (COVID-19). While B-cell memory is the hallmark of serological immunity, its role in driving successful vaccine responses and providing immune protection in SOT patients remains unclear. Methods: We investigated the function and interplay of SARS-CoV-2-specific memory B cells (mBc), different cytokineproducing T cells, and cross-reactive NAb in driving seroconversion and protection against COVID-19 in two cohorts. First, we studied a large cohort of 148 SOT recipients and 32 immunocompetent individuals who underwent several vaccinations. Subsequently, we assessed 25 SOT patients participating in a randomized controlled trial to compare two different immunosuppressive strategies for allowing successful seroconversion and memory-cell responses after booster vaccination. Results: We corroborate previous findings that B- and T-cell memory responses are weaker and more delayed in SOT patients than in immunocompetent (IC) individuals; however, within the SOT cohort, we found that these responses are relatively stronger and more robust in patients not receiving mycophenolate mofetil (MMF)-based therapies. Anti-spike IgG titers strongly correlated with RBD-specific IgG-producing mBc, with both displaying broad viral cross reactivity. Prebooster SARS-CoV-2-specific mBc and IL-2-producing T cells accurately predicted Nab seroconversion (AUC, 0.828) and protection against severe COVID-19. While switching unresponsive SOT patients from calcineurin inhibitors (CNI)/MMF to a low-exposure CNI/mTOR-i regimen favored wider SARS-CoV-2-specific immune responses after a fourth booster vaccination, preformed RBD-specific mBc predicted NAb seroconversion. Discussion: Our study adds new insights into the pathobiology of immune memory and highlights the pivotal role of SARS-CoV-2-specific mBc in promoting immune protection inSOT patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Rabbit hemorrhagic disease virus 2 (RHDV2) was reported in the United States in 2018 and has since spread across most of the country where it has a potential for adverse impacts on ecosystems, economic losses, and pet rabbit health. Using an emergency use authorized vaccine, seroconversion and protection was demonstrated in 3- to 7-week-old specific pathogen free laboratory rabbits. The purpose of the current study was to examine this protocol in pet rabbits, which would be inclusive of varied breeds and ages. Importantly, no significant differences were observed in routine clinical pathology measures. Seroconversion was also observed but was variable, and lower levels of seroconversion were associated with increased age. In general, while variable outcomes to vaccination are expected, these preliminary data underlie the importance of examining the response of pet rabbits to help optimize new vaccine protocols. We propose this will complement traditional vaccine studies, aid in maintaining the health of pet rabbits, and help in the ultimate control of this highly infectious virus. A recombinant vaccine for rabbit hemorrhagic disease virus 2, a highly pathogenic virus, was granted emergency use authorization in the United States after the detection and spread of the virus starting in 2018. The goal of the current study was to assess pet rabbits (n = 29) through physical examination and routine clinical pathology testing using repeated assessments post-vaccination. In addition, seroconversion was also monitored after the initial vaccination and booster vaccination. Neither owners nor clinicians detected any physical abnormalities in relationship to the vaccine protocol. Hematological and clinical biochemistry testing showed some changes although median values were within species specific reference intervals. A significant increase in antibody levels was observed at day 21 (post-initial vaccination) and day 49 (post-booster vaccination) versus that present at baseline (p < 0.0001). However, variability in study rabbits was noted with some individuals showing low antibody levels as well as a lower overall response in older rabbits (r = −0.56, p = 0.006). A second cohort of rabbits was assessed at 11–12 months post-initial vaccination. In this second group, antibody levels were not significantly different from baseline levels (p = 0.21). Additional studies should be conducted to further define the variability in seroconversion and the term of protection in pet rabbits as the industry moves forward in the optimization of RHDV2 vaccines. [ABSTRACT FROM AUTHOR]

Background Bivalent messenger RNA (mRNA) vaccines, designed to combat emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, incorporate ancestral strains and a new variant. Our study assessed the immune response in previously vaccinated individuals of the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS) following bivalent mRNA vaccination. Methods Eligible SHCS and STCS participants received approved bivalent mRNA SARS-CoV-2 vaccines (mRNA-1273.214 or BA.1-adapted BNT162b2) within clinical routine. Blood samples were collected at baseline, 4 weeks, 8 weeks, and 6 months postvaccination. We analyzed the proportion of participants with anti-spike protein antibody response ≥1642 units/mL (indicating protection against SARS-CoV-2 infection), and in a subsample T-cell response (including mean concentrations), stratifying results by cohorts and population characteristics. Results In SHCS participants, baseline anti-spike antibody concentrations ≥1642 units/mL were observed in 87% (96/112), reaching nearly 100% at follow-ups. Among STCS participants, 58% (35/60) had baseline antibodies ≥1642 units/mL, increasing to 80% at 6 months. Except for lung transplant recipients, all participants showed a 5-fold increase in geometric mean antibody concentrations at 4 weeks and a reduction by half at 6 months. At baseline, T-cell responses were positive in 96% (26/27) of SHCS participants and 36% (16/45) of STCS participants (moderate increase to 53% at 6 months). Few participants reported SARS-CoV-2 infections, side-effects, or serious adverse events. Conclusions Bivalent mRNA vaccination elicited a robust humoral response in individuals with human immunodeficiency virus (HIV) or solid organ transplants, with delayed responses in lung transplant recipients. Despite a waning effect, antibody levels remained high at 6 months and adverse events were rare. Clinical Trials Registration. NCT04805125. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) causes substantial respiratory disease. Bivalent RSV prefusion F (RSVpreF) vaccine is licensed in ≥60-year-olds. RSVpreF was well tolerated and immunogenic in a phase 1/2 study. We evaluated antibody persistence after initial vaccination and safety and immunogenicity after revaccination from this study. Methods Healthy adults were randomized to receive initial vaccination and revaccination 12 months later with either placebo or RSVpreF (240 µg with or without aluminum hydroxide). RSV-A and RSV-B geometric mean neutralizing titers (GMTs) were measured through 12 months after both vaccinations. Tolerability and safety were assessed. Results There were 263 participants revaccinated (18–49 years old, n = 134; 65–85 years old, n = 129). Among 18- to 49-year-olds and 65- to 85-year-olds, geometric mean fold rises (GMFRs) for both RSV subgroups (RSV-A, RSV-B) 1 month after initial RSVpreF vaccination were 13.3 to 20.4 and 8.9 to 15.5, respectively, as compared with levels before initial vaccination; corresponding GMFRs 12 months after initial vaccination were 4.1 to 5.0 and 2.6 to 4.1. GMFRs 1 month after revaccination vs levels before revaccination were 1.4 to 2.3 and 1.4 to 2.2 for 18- to 49-year-olds and 65- to 85-year-olds. Peak GMTs after revaccination were lower than those after initial vaccination. GMTs 12 months after initial vaccination and revaccination were similar, with GMFRs ranging from 0.7 to 1.6. No safety signals occurred. Conclusions RSVpreF revaccination was immunogenic and well tolerated among adults. Clinical Trials Registration. NCT03529773 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

Background: Older persons elicit heterogeneous antibody responses to vaccinations that generally are lower than those in younger, healthier individuals. As older age and certain comorbidities can influence these responses we aimed to identify health-related variables associated with antibody responses after repeated SARS-CoV-2 vaccinations and their persistence thereafter in SARS-CoV-2 infection-naïve and previously infected older persons. Method: In a large longitudinal study of older persons of the general population 50 years and over, a sub-cohort of the longitudinal Doetinchem cohort study (n = 1374), we measured IgG antibody concentrations in serum to SARS-CoV-2 Spike protein (S1) and Nucleoprotein (N). Samples were taken following primary vaccination with BNT162b2 or AZD1222, pre- and post-vaccination with a third and fourth BNT162b2 or mRNA-1273 (Wuhan), and up to a year after a fifth BNT162b2 bivalent (Wuhan/Omicron BA.1) vaccine. Associations between persistence of antibody concentrations over time and age, sex, health characteristics including cardiometabolic and inflammatory diseases as well as a frailty index were tested using univariable and multivariable models. Results: The booster doses substantially increased anti-SARS-CoV-2 Spike S1 (S1) antibody concentrations in older persons against both the Wuhan and Omicron strains. Older age was associated with decreased antibody persistence both after the primary vaccination series and up to 1 year after the fifth vaccine dose. In infection-naïve persons the presence of inflammatory diseases was associated with an increased antibody response to the third vaccine dose (Beta = 1.53) but was also associated with reduced persistence over the 12 months following the fifth (bivalent) vaccine dose (Beta = -1.7). The presence of cardiometabolic disease was associated with reduced antibody persistence following the primary vaccination series (Beta = -1.11), but this was no longer observed after bivalent vaccination. Conclusion: Although older persons with comorbidities such as inflammatory and cardiometabolic diseases responded well to SARS-CoV-2 booster vaccinations, they showed a reduced persistence of these responses. This might indicate that especially these more vulnerable older persons could benefit from repeated booster vaccinations. [ABSTRACT FROM AUTHOR]

Background: We explored vaccine motivation and preferences for tick-borne encephalitis (TBE) vaccine attributes among participants in TBE-endemic countries in Europe. Methods: An online survey was conducted among the general public in Austria, Germany, Switzerland, and Sweden. Participants were ≥ 18 years old, open to receiving vaccines, and living in, or regularly traveling to, TBE-endemic regions in the aforementioned countries. Participants were asked about their general vaccine knowledge and motivations for vaccination, before rating the importance of TBE vaccine attributes, such as efficacy, safety, dosing schedule, and booster interval. Thereafter, participants were shown three hypothetical TBE vaccine profiles with different combinations of attributes. Assuming equal efficacy and safety, participants were asked to select their preferred profile from 12 screens as part of a discrete-choice conjoint analysis. Utility scores were calculated to show the importance of each attribute. Data are presented for the overall survey group and by age and gender, using t-tests to compare means. Results: For 73% of participants (n = 1003/1379), self-protection was among the top three reasons to get vaccinated. Disease severity, protection of children or family, and advice or recommendation from a doctor/healthcare professional (HCP) were top three reasons for over half of participants. The majority (58–69%) agreed or strongly agreed that they trust their doctor/HCP on the subject of vaccines, they rely on their doctor/HCP's vaccine knowledge, and they prefer their doctor/HCP to make recommendations on which vaccines they or their families should take. Efficacy and safety were the most important standalone TBE vaccine attributes; however, among TBE vaccine profiles including 3-, 5- and 10-year booster intervals, the 10-year booster interval was the most influential attribute level when choosing a preferred vaccine profile (utility score: 0.58 [standard error: 0.01]). Differences in motivators and preferences were observed between age and gender subgroups. Conclusion: The high level of doctor/HCP reliance highlights the key role doctors/HCPs play in influencing vaccine decision-making. Booster interval was the biggest driver of choice when selecting a hypothetical TBE vaccine profile, with the strongest preference for a 10-year booster interval. These findings could be used to inform TBE vaccination recommendations and in the further development of TBE vaccines. [ABSTRACT FROM AUTHOR]

WHO currently recommends a single dose of typhoid conjugate vaccine (TCV) in high-burden countries based on 2-year vaccine efficacy data from large randomised controlled trials. Given the decay of immunogenicity, the protection beyond 2 years is unknown. We therefore extended the follow-up of the TyVAC trial in Bangladesh to assess waning of vaccine protection to 5 years after vaccination. We conducted a cluster randomised controlled trial (TyVAC; ISRCTN11643110) in Dhaka, Bangladesh, between 2018 and 2021. Children aged 9 months to 15 years were invited to receive a single dose of TCV or Japanese encephalitis vaccine between April 15, 2018, and November 16, 2019, based on the randomisation of their clusters of residence. Children who received the Japanese encephalitis vaccine were invited to receive TCV at the final visit between Jan 6, and Aug 31, 2021, according to the protocol. This follow-on study extended the follow-up of the original trial until Aug 14, 2023. The primary endpoint of this study was to compare the incidence of blood culture-confirmed typhoid between children who received TCV in 2018–19 (the previous-TCV group) and those who received the vaccine in 2021 (the recent-TCV group), to evaluate the relative decline in vaccine protection. We also did a nested study using the test-negative design comparing the recent-TCV and previous-TCV groups with unvaccinated individuals, as well as an immunogenicity study in a subset of 1500 children. Compared with the recent-TCV group, the previous-TCV group had an increased risk of typhoid fever between 2021–23, with an adjusted incidence rate ratio of 3·10 (95% CI 1·53 to 6·29; p<0·0001), indicating a decline in the protection of a single-dose of TCV 3–5 years after vaccination. The extrapolated vaccine effectiveness in years 3–5 was 50% (95% CI –13 to 78), and was validated using the test-negative design analysis, with a vaccine effectiveness of 84% (74 to 90) in the recent-TCV group and 55% (36 to 68) in the previous-TCV group, compared with unvaccinated individuals. Anti-Vi-IgG responses declined over the study period. The highest rate of decay was seen in children vaccinated at younger than 2 years in the original trial. The inverse correlation between age and the decay of antibodies was also seen in the subgroup analysis of vaccine effectiveness, where the youngest age group (<7 years at fever visits) exhibited the fastest waning, with vaccine effectiveness dropping to 24% (95% CI –29 to 55) at 3–5 years after vaccination. A decline in the protection conferred by a single-dose TCV was observed 3–5 years after vaccination, with the greatest decline in protection and immune responses observed in children vaccinated at younger ages. A booster dose of TCV around school entry age might be needed for children vaccinated while younger than 2 years to sustain protection against typhoid fever during the school years when the risk is the highest. The Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

Residents in nursing homes face heightened COVID-19 risks. We aimed to assess the adverse events (AEs) rates and antibody responses after the first to the fifth dose of COVID-19 mRNA vaccination in a nursing home cohort. Ninety-five SARS-CoV-2 naïve participants consisted of 26 staff (median age, 51 years) and 69 residents (median age, 88 years). Life-threatening AEs were reported in neither residents nor staff. The severity of non-life-threatening AEs was graded, and severe AEs were reported only in staff. The AEs rates were considerably lower in residents, compared to those in staff. Anti-RBD IgG and the neutralizing titers (NTs) against Wuhan and Omicron BA.4/BA.5 did not differ significantly between those with 'any AE' and 'no AE' among both staff and residents two months after the second, third and fifth doses, while the anti-RBD IgG significantly differed between two groups after third dose in residents. These findings suggest that the anti-RBD IgG and the NTs increase regardless of the occurrence of AEs. Our study underscores a robust antibody response in both in staff and residents, and fewer AEs following COVID-19 vaccination in SARS-CoV-2 naïve residents than staff, supporting the recommendation for mRNA booster doses in older adults at high-risk care facilities. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Hematopoietic cell transplant (HCT) survivorship care includes recommendations for post‐HCT revaccination to restore immunity to vaccine‐preventable diseases (VPDs). However, not all survivors agree to be vaccinated. No existing studies have comprehensively reported barriers and facilitators to adult HCT survivors completing revaccination.A cross‐sectional survey of 194 adult HCT survivors was analyzed using convergent mixed methods. The analysis used various statistical methods to determine the prevalence of barriers and facilitators and the association between revaccination and the number and specific type of barriers and facilitators. Content analysis was applied to open‐ended item responses. Integrated analysis merged quantitative and qualitative findings.The most frequent barriers included the inability to receive live vaccines because of immunosuppression, identifying a suitable community location for administering childhood vaccines to adults, and delayed immune recovery. The most frequent facilitators were having healthcare insurance and a clear calendar of the revaccination schedule. Complete revaccination rates were lower with each additional reported barrier (OR = 0.58; 95% CI 0.459–0.722) and higher with each additional reported facilitator (OR = 1.31; 95% CI 1.05–1.63). Content analysis suggested that most barriers were practical issues. One significant facilitator highlighted by respondents was for the transplant center to coordinate and serve as the vaccination location for revaccination services. Merged analysis indicated convergence between quantitative and qualitative data.Practical barriers and facilitators played a consequential role in revaccination uptake, and survivors would like to be revaccinated at the transplant center. [ABSTRACT FROM AUTHOR]

We aimed to understand the temporal dynamics of SARS‐CoV‐2 reinfection risk and assess the impact of inactivated vaccination on the occurrence of reinfection. We investigated the reinfection risk of SARS‐CoV‐2 from November 1, 2022, to February 12, 2023, when China rapidly lifted the zero‐COVID policy. The study subjects were those who were first infected during the zero‐COVID period between January 1, 2020, and October 31, 2022, in Dalian city, China. Among the 1961 previous infections, 126 (6.4%, 95% CI: 5.4, 7.5) were reinfected. The risk of reinfection increased over time since initial infection. Compared with those who did not receive or received one dose of inactivated vaccine, receiving two or three doses was associated with additional protection against reinfection among individuals who were infected with pre‐Omicron more than a year earlier, with the OR ranged from 0.33 (95% CI: 0.03, 1.83) to 0.91 (95% CI: 0.22, 3.27). In contrast, no protective effect from two or three doses of vaccines against reinfection was observed among those who were first infected with Omicron variants within a year. Primary or booster vaccination contributed to limited protection against reinfection or symptomatic reinfection among individuals infected with Omicron SARS‐CoV‐2 within a year. However, a booster dose after 1 year of natural infection may provide additional protection against reinfection. [ABSTRACT FROM AUTHOR]

Background: Omicron variants have rapidly diversified into sublineages with mutations that enhance immune evasion, posing challenges for vaccination and antibody responses. This study aimed to compare serum cross‐neutralizing antibody responses against various SARS‐CoV‐2 Omicron sublineages (BA.1, BA.5, XBB.1.17.1, FK.1.1, and JN.1) in recipients of monovalent COVID‐19 boosters, bivalent booster recipients, and individuals who had recovered from Omicron BA.5 infections. Methods: We conducted a micro‐neutralization assay on serum samples from monovalent BNT162b2 booster recipients (N = 54), bivalent BNT162b2 booster recipients (N = 24), and SARS‐CoV‐2 Omicron BA.5‐recovered individuals (N = 13). The history of SARS‐CoV‐2 Omicron infection was assessed using ELISA against the SARS‐CoV‐2 NP protein. Results: Bivalent booster recipients exhibited significantly enhanced neutralization efficacy against Omicron sublineages compared to those who had received monovalent booster vaccinations. Omicron BA.5‐recovered individuals displayed similar neutralizing antibodies (NAbs) to the bivalent booster recipients. Despite the improved neutralization in bivalent recipients and BA.5‐recovered individuals, there were limitations in neutralization against the recently emerged Omicron subvariants: XBB.1.17.1 FK.1.1, and JN.1. In both monovalent and bivalent booster recipients, a history of Omicron breakthrough infection was associated with relatively higher geometric mean titers of NAbs against Omicron BA.1, BA.5, and XBB.1.17.1 variants. Conclusion: This study underscores the intricate interplay between vaccination strategies, immune imprinting, and the dynamic landscape of SARS‐CoV‐2 variants. Although bivalent boosters enhance neutralization, addressing the challenge of emerging sublineages like XBB.1.17.1, FK.1.1, and JN.1 may necessitate the development of tailored vaccines, underscoring the need for ongoing adaptation to effectively combat this highly mutable virus. [ABSTRACT FROM AUTHOR]

Background: This study provides a head‐to‐head comparison of the protection provided by the BNT162b2 and mRNA‐1273 vaccines against SARS‐CoV‐2 infection and against severe COVID‐19, covering primary series and third dose/booster vaccinations over up to 3 years of follow‐up, both before and after the emergence of the omicron variant. Methods: Two national, matched, retrospective cohort studies were conducted on Qatar's vaccinated population from December 16, 2020, to February 18, 2024. Subgroup analyses by pre‐vaccination SARS‐CoV‐2 infection history, as well as sensitivity analyses, were also conducted. Results: The adjusted hazard ratio (AHR) comparing infection incidence in those vaccinated with BNT162b2 versus mRNA‐1273 was 1.03 (95% CI: 1.02–1.05) after the primary series and 1.11 (95% CI: 1.09–1.13) after the third (booster) dose. The corresponding AHRs for any severe, critical, or fatal COVID‐19 were 1.31 (95% CI: 0.81–2.11) and 1.00 (95% CI: 0.20–4.94), respectively. Subgroup analyses by prior infection status hinted at a dose‐dependent immune imprinting effect, where a combination of two types of immunity, pre‐omicron and omicron, offered greater protection against infection than one type alone, with this effect being amplified by the higher antigen dose of mRNA‐1273 compared to BNT162b2. Sensitivity analyses confirmed the study findings. Conclusions: BNT162b2 provided slightly less protection against infection than mRNA‐1273 following both primary series and booster vaccinations while offering comparable protection against severe COVID‐19 outcomes. The findings suggested that the vaccine antigen dose in interaction with infection history may determine the extent of immune protection against infection. [ABSTRACT FROM AUTHOR]

Background: In recent years, Europe has experienced a significant increase in pertussis cases. One reason behind this rise is the decline in diphtheria–tetanus–pertussis (dTap) booster coverage among adults. Currently, Italy lacks a reliable monitoring system to track pertussis infections and vaccine coverage among adults. We therefore evaluated the reliability of a primary care framework to respond to this need. Methods: Using an Italian primary care database for individuals aged 15 or above, we determined the pertussis infection notification rate and dTap vaccine/booster coverage for the timeframe of 2009–2022. Results: In the overall population, we obtained a lifetime occurrence rate of pertussis infections of 7.52 per 10,000 individuals. The annual incidence rates of pertussis infections ranged from 0.008 to 0.001 per 10,000 person-years between 2009 and 2022. A rising trend in dTap vaccine coverage rate (ranging from 8.72 to 16.54 vaccines per 10,000 individuals) was observed during the same period. Notably, those aged 65 or older, smokers, and/or individuals with immunodeficiencies were more likely to receive the dTap vaccine compared to the general population. Conclusions: Given the organization of the Italian public health system, this primary care network might act as a reliable epidemiological monitoring system to keep track of pertussis infections and dTap vaccine coverage in adults. Pertussis cases were underreported, and there was a low uptake of vaccines and boosters. Therefore, it is crucial to closely monitor pertussis notifications and dTap administrations and develop intervention strategies at the national level to enhance vaccine-related prevention. [ABSTRACT FROM AUTHOR]

A correction notice was issued for a study on severe COVID-19 outcomes in five Latin American countries in the post-vaccination era, addressing an error in reported hospitalized cases in Brazil. The study analyzed clinical profiles, hospitalization rates, mortality rates, and vaccination status of confirmed COVID-19 cases, highlighting differences in outcomes between males and age groups, as well as the impact of comorbidities and COVID-19 variants on hospitalization rates. Detailed data on COVID-19 cases, mortality rates, ICU admissions, comorbidities, and vaccination status by age group is provided for Brazil, Mexico, Colombia, Argentina, and Chile, offering insights into the pandemic's impact in different regions. The authors have made corrections to ensure the scientific accuracy of their conclusions. [Extracted from the article]

Background: Zika virus (ZIKV) is an emerging public health threat, rendering development of a safe and effective vaccine against the virus a high priority to face this unmet medical need. Our vaccine candidate has been developed on the same platform used for the licensed vaccine IXIARO®, a vaccine against Japanese Encephalitis virus, another closely related member of the Flaviviridae family.Methods: Between February 24, 2018 and November 16, 2018, we conducted a randomized, observer-blinded, placebo controlled, single center phase 1 study to assess the safety and immunogenicity of an adjuvanted, inactivated, purified whole-virus Zika vaccine candidate in the U.S. A total of 67 healthy flavivirus-naïve adults aged 18 to 49 years were randomly assigned to one of five study arms to receive two immunizations of either high dose or low dose (6 antigen units or 3 antigen units) with both dose levels applied in two different immunization regimens or placebo as control.Results: Our vaccine candidate showed an excellent safety profile independent of dose and vaccination regimen with predominantly mild adverse events. No serious adverse event has been reported. The ZIKV vaccine induced neutralizing antibodies in all tested doses and regimens with seroconversion rates up to 85.7% (high dose), which remained up to 40% (high dose) at 6 months follow-up. Of note, the rapid regimen triggered a substantial immune response within days.Conclusions: The rapid development and production of a ZIKV vaccine candidate building on a commercial Vero-cell manufacturing platform resulted in a safe and immunogenic vaccine suitable for further clinical development. To optimize antibody persistence, higher doses and a booster administration might be considered. [ABSTRACT FROM AUTHOR]

Annual vaccination is widely recommended for influenza and SARS‐CoV‐2. In this essay, we analyse and question the prevailing policymaking approach to these respiratory virus vaccines, especially in the United States. Every year, licensed influenza vaccines are reformulated to include specific strains expected to dominate in the season ahead. Updated vaccines are rapidly manufactured and approved without further regulatory requirement of clinical data. Novel vaccines (i.e. new products) typically undergo clinical trials, though generally powered for clinically unimportant outcomes (e.g. lab‐confirmed infections, regardless of symptomatology or antibody levels). Eventually, the current and future efficacy of influenza and COVID‐19 vaccines against hospitalization or death carries considerable uncertainty. The emergence of highly transmissible SARS‐CoV‐2 variants and waning vaccine‐induced immunity led to plummeting vaccine effectiveness, at least against symptomatic infection, and booster doses have since been widely recommended. No further randomized trials were performed for clinically important outcomes for licensed updated boosters. In both cases, annual vaccine effectiveness estimates are generated by observational research, but observational studies are particularly susceptible to confounding and bias. Well‐conducted experimental studies, particularly randomized trials, are necessary to address persistent uncertainties about influenza and COVID‐19 vaccines. We propose a new research framework which would render results relevant to the current or future respiratory viral seasons. We demonstrate that experimental studies are feasible by adopting a more pragmatic approach and provide strategies on how to do so. When it comes to implementing policies that seriously impact people's lives, require substantial public resources and/or rely on widespread public acceptance, high evidence standards are desirable. [ABSTRACT FROM AUTHOR]

A 16-year-old patient, while an infant, incurred right-sided hemiparesis and had difficulty breast feeding. She was later diagnosed with a neonatal stroke and her genetic testing showed a missense mutation in her PROS1 (Protein S) gene. Both her grandfather and father, but not her mother, had hereditary Protein S (PS) deficiency. The patient was not prescribed any mediation due to her young age but was frequently checked by her physician. The patient's plasma was first collected at the age of 13, and the isolated plasma from the patient and her father were analyzed by aPTT, thrombin generation, and enzyme-linked immunosorbent assays. These analyses showed low PS activity and clotting time associated with the missense mutation in the PROS1 gene. During the COVID-19 pandemic, the patient received her first Pfizer vaccination dose in 2021, followed by a booster dose in 2022. The plasma samples were collected 8 weeks post-immunization, after which her clotting parameters had improved for up to 6 months following vaccination. The patient's plasma showed a significant reduction in thrombin generation and an improved aPTT clotting time. Mass spectrometry analysis revealed that her antithrombin-III level was significantly higher post-vaccination, and both thrombin and FXII levels were significantly lowered compared with her father. To our knowledge, this is the first report to document that COVID-19 vaccination can lower the risk of thrombosis in a patient with inherited thrombophilia. Although the effect was observed on a single mutation, it would be interesting to investigate the effect of COVID-19 vaccinations on other thrombophilia. [ABSTRACT FROM AUTHOR]

With two endorsed and prophylactic vaccines against Zaire ebolavirus (referred to hereafter as EBOV), the number of individuals vaccinated against EBOV worldwide is estimated to range between 500 000 and 1 000 000 individuals, increasing with every renewed EBOV threat and vaccination campaign. Therefore, re-exposure of previously vaccinated health-care workers, and possibly community members, could become more frequent. In the absence of long-term data on vaccine efficacy and duration of protection, we urgently need to understand revaccination strategies that could maximise the level of protection. In this Personal View, we highlight the scarcity of available evidence to guide revaccination recommendations for the accumulating groups of previously vaccinated communities or front-line health-care workers that could be redeployed or re-exposed in the next EBOV outbreak(s). This evidence base is crucial to identify optimal target populations and the frequency of booster doses, and guide vaccine interchangeability (especially in settings with limited or unpredictable vaccine supplies), while preventing vaccine mistrust, equity concerns, and exclusion of vulnerable populations. We discuss five priority gaps (to whom, when, and how frequently, to provide booster doses; long-term correlates and thresholds of protection; the effect of vector-directed immunity and viral variant protection; comparative research in mix-and-match schedules; and implementation concerns) that should be urgently tackled to adapt the initial EBOV prophylactic vaccination strategies considering potential booster dose vaccinations. [ABSTRACT FROM AUTHOR]

This letter to the editor raises concerns about a systematic review and meta-analysis comparing the vaccine effectiveness of mRNA-1273 and BNT162b2 COVID-19 vaccines in adults aged 50 and older. The authors argue that the meta-analysis was flawed because it used crude data instead of adjusted estimates, leading to incorrect conclusions and exaggerated differences in vaccine effectiveness. They also criticize the inclusion of studies that were not head-to-head comparisons and the reliance on outdated data that does not reflect the current state of population immunity against SARS-CoV-2. The authors conclude that recent studies during the Omicron era have shown no difference in effectiveness between the two vaccines. [Extracted from the article]

Background: The safety profile of COVID-19 vaccines in immunocompromised patients has not been comprehensively evaluated. Aim: To measure the frequency of patient-reported adverse drug reactions (ADRs) related to the first/second/booster dose of COVID-19 vaccine in immunocompromised subject versus matched cohort. As a secondary objective, the time course, evaluated as time to onset (TTO) and time to recovery (TTR), of COVID-19 vaccine-related ADRs was explored. Methods: A prospective cohort study, based on electronic questionnaires filled by vaccinees from 11 European countries in the period February 2021 to February 2023 was conducted. All immunocompromised vaccinees who provided informed consent and registered to the project's web-app within 48 h after first/booster vaccine dose administration of any EMA-authorised COVID-19 vaccine were recruited. Participants filled baseline and up to six follow-up questionnaires (FU-Qs) over 6 months from vaccination, collecting information on suspected COVID-19 vaccine-related ADRs. As a control group, non-immunocompromised vaccinees from the same source population were 1:4 matched by sex, age, vaccine dose, and brand. A descriptive analysis of demographic/clinical characteristics of vaccinees was conducted. Heatmaps of the frequency of solicited ADRs, stratified by gender and vaccine brand, were generated. Median TTO/TTR of reported ADRs were visualised using violin/box-plots. Results: A total of 773 immunocompromised vaccines were included in the analyses. Most participants were females (F/M ratio: 2.1 and 1.6) with a median age of 56 (43–74) and 51 (41–60) years, at the first vaccination cycle and booster dose, respectively. Injection-site pain and fatigue were the most frequently reported ADRs in immunocompromised vaccinees with higher frequency than matched control, especially after the first dose (41.2% vs 37.8% and 38.2% vs 32.9%, respectively). For both cohorts, all solicited ADRs were more frequently reported in females than males, and in those who had received a first dose of the Vaxzevria vaccine. Dizziness was the most frequently reported unsolicited ADR after the first dose in both groups (immunocompromised subjects: 2.5% and matched controls: 2.1%). At the booster dose, lymphadenopathy (3.9%) and lymphadenitis (1.8%) were the most reported unsolicited ADRs for immunocompromised subjects and matched controls, respectively. A very low number of subjects reported adverse event of special interest (AESI) (2 immunocompromised, 3 matched controls) and serious ADRs (5 immunocompromised, 5 matched controls). A statistically significant difference among study cohorts was observed for median TTO after the booster dose, and for median TTR after the first vaccination cycle and booster dose (p < 0.001). Conclusion: The overall safety profile of COVID-19 vaccines in immunocompromised people was favourable, with minor differences as compared to non-immunocompromised vaccinees. Participants mostly experienced mild ADRs, mainly reported after the first dose of Vaxzevria and Jcovden vaccines. Serious ADRs and AESI were rare. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic posed significant challenges worldwide, with SARS-CoV-2 vaccines critical in reducing morbidity and mortality. This study evaluates the immunogenicity and antibody persistence of the BNT162b2 vaccine in people living with HIV (PLWH). Methods: We monitored anti-SARS-CoV-2 Spike IgG concentration in a cohort of PLWH at five time points (T0–T4) using chemiluminescent microparticle immunoassays (CMIAs) at the baselined both during and after vaccination. In severely immunocompromised individuals, a boosting dose was recommended, and participants and IgG concentration were measured in the two subgroups (boosted and not boosted). Results: In total, 165 PLWH were included, and 83% were male with a median age of 55 years (IQR: 47–62). At T1, 161 participants (97.6%) showed seroconversion with a median of IgG values of 468.8 AU/mL (IQR: 200.4–774.3 AU/mL). By T2, all subjects maintained a positive result, with the median anti-SARS-CoV-2 Spike IgG concentration increasing to 6191.6 AU/mL (IQR: 3666.7–10,800.8 AU/mL). At T3, all participants kept their antibody levels above the positivity threshold with a median of 1694.3 AU/mL (IQR: 926.3–2966.4 AU/mL). At T4, those without a booster dose exhibited a marked decrease to a median of 649.1 AU/mL (IQR: 425.5–1299.8 AU/mL), whereas those with a booster experienced a significant increase to a median of 13,105.2 AU/mL (IQR: 9187.5–18,552.1 AU/mL). The immune response was negatively influenced by the presence of dyslipidaemia at T1 (aOR 4.75, 95% CI: 1.39–16.20) and diabetes at T3 (aOR 7.11, 95% CI: 1.10–46.1), while the use of protease inhibitors (aORs 0.06, 95% CI: 0.01–0.91) and being female (aOR 0.02, 95% CI: 0.01–0.32) at T3 were protective factors. Conclusions: The immunogenicity of the BNT162b2 vaccine in PLWH has been confirmed, with booster doses necessary to maintain high levels of anti-SARS-CoV-2 Spike IgG antibodies, especially in patients with comorbidities. These findings underline the importance of a personalized vaccination strategy in this population. [ABSTRACT FROM AUTHOR]

Introduction: As the COVID-19 pandemic becomes an endemic state, still many questions remain regarding the risks and impact of SARS-CoV-2 infection and vaccination in patients with immune-mediated inflammatory diseases (IMIDs) who were excluded from the phase 3 COVID-19 vaccination trials. Methods: The BELCOMID study collected patient data and serological samples from a large, multicentric IMID patient cohort that was prospectively followed during sequential stages of the pandemic. Patients were stratified according to vaccination status into five groups across three sampling periods. Interactions between SARS-CoV-2 infection, COVID-19 vaccination status, IMID-treatment modalities and IMID course were explored. Results: In total, 2165 patients with IBD, a dermatological or rheumatological IMID participated. SARS-CoV-2 infection rates increased over the course of the pandemic and were highest in IMID patients that had refused every vaccine. After baseline COVID-19 vaccination, serologic spike (S)-antibody responses were attenuated by particular types of immune-modulating treatment: anti-TNF, rituximab, JAKi, systemic steroids, combined biologic/immunomodulator treatment. Nonetheless, S-antibody concentration increased progressively in patients who received a booster vaccination, reaching 100% seroconversion rate in patients who had received two booster vaccines. Previous SARS-CoV-2 infection was found as a predictor of higher S-antibody response. Patients who had refused every vaccine showed the lowest rates of S-seroconversion (53.8%). Multiple logistic regression did not identify previous SARS-CoV-2 infection as a risk factor for IMID flare-up. Furthermore, no increased risk of IMID flare-up was found with booster vaccination. Conclusions: Altogether, the BELCOMID study provides evidence for the efficacy and safety of COVID-19 vaccination and confirms the importance of repeated booster vaccination in IMID patients. [ABSTRACT FROM AUTHOR]

Background: The 2019 coronavirus disease (COVID-19) pandemic induced a major health crisis worldwide, notably among end-stage kidney disease (ESKD) patients. Vaccination against SARS-CoV-2, especially with messenger RNA (mRNA) vaccines, is highly effective and reduces hospitalization and mortality in both the general and ESKD populations. Age and previous COVID-19 infection have been identified as major determinants of the vaccine response in both the general population and ESKD patients. Methods: To determine the specific phenotype of ESKD patients in relation to their vaccine response, a clustering approach was used in a cohort of 117 fully vaccinated patients. Results: Clustering revealed three distinct clinical phenotypes among hemodialysis patients in terms of immunological response. Two clusters, consisting of either women with a long dialysis history or male subjects with diabetes with a moderate history of dialysis, exhibited low levels of IgG anti-spike antibodies. The third cluster consisted of non-diabetic middle-aged men with a moderate dialysis vintage and a very good serological response to vaccination. Conclusions: These vaccinal phenotypes of dialysis patients are easily identifiable in current practice, allowing for differential serological follow-up and tailored booster SARS-CoV-2 vaccination. [ABSTRACT FROM AUTHOR]

The SARS-CoV-2 evolution trajectory remains uncertain, and the antigenic characteristics of future variants are highly unpredictable. We report the immunogenicity and safety of multivalent COVID-19 vaccines, SCTV01E and SCTV01E-1, against Omicron BA.5. This phase 2 trial randomized 400 adults into two cohorts, 160 unvaccinated (3 doses) and 240 previously vaccinated (2 doses) individuals to receive 30 µg SCTV01E-1 or 30 µg SCTV01E (1:1) between 4 November and 28 November 2022. Among the unvaccinated cohort, day 42 geometric mean fold rises (GMFRs) of neutralizing antibodies (nAb) against Omicron BA.5 were reported to be 12.8× and 20.5× over day 0 for SCTV01E-1 and SCTV01E, respectively. On day 178, both vaccines increased geometric mean titers (GMTs) of nAb against BA.5 following the booster dose compared to pre-booster levels on D150. Similar frequencies of solicited [6.2% (5/81) and 7.6% (6/79)] and unsolicited [11.1% (9/81) and 10.1% (8/79)] adverse events (AEs) were reported in SCTV01E-1 and SCTV01E groups, respectively. Grade 3 or more AEs were < 2% in both vaccine groups [SCTV01E-1: 1.2% (1/81), SCTV01E: 1.3% (1/79)]. In the previously vaccinated cohort, similar GMFRs were reported on day 28 (SCTV01E-1: 9.4× and SCTV01E: 8.7×) over baseline (D0). On day 148, both vaccines showed increased nAb levels with similar GMFRs over D120. Comparable incidences of solicited [13.2% (16/121) and 10.9% (13/119)] and unsolicited [17.4% (21/121) and 10.9% (13/119)] AEs were reported in SCTV01E-1 and SCTV01E groups, respectively. Numerically identical ≥ grade 3 AEs [SCTV01E-1: 1.7% (2/121) and SCTV01E: 1.7% (2/119)] were reported. This trial demonstrates the effectiveness of updated multivalent vaccines with acceptable safety profiles. [ABSTRACT FROM AUTHOR]

Understanding variables that influence antibody responses to COVID-19 vaccination within a population can provide valuable information on future vaccination strategies. In this population-based study, we examined the antibody responses to COVID-19 vaccination in Manitoba using residual serum specimens collected between January 2021 and March 2022 (n = 20,365). Samples were tested for spike and nucleocapsid IgG against SARS-CoV-2 using clinically validated assays. We assessed the impacts of multiple factors on post-vaccination antibody titres including type of vaccine, age, sex, geographic location, number of doses received, and timing of vaccination. Our investigation demonstrated that vaccination with one dose of Moderna mRNA-1273 elicited higher anti-spike IgG titres overall compared to Pfizer BNT162b2 vaccination, while one dose of Pfizer BNT162b2 followed by a second dose of Moderna mRNA-1273 exhibited higher titres than two doses of Pfizer BNT162b2 or Moderna mRNA-1273, irrespective of age. Age and time post-vaccination had considerable effects on antibody responses, with older age groups exhibiting lower anti-spike IgG titres than younger ages, and titres of those vaccinated with Pfizer BNT162b2 waning faster than those vaccinated with Moderna mRNA-1273 or a combination of Pfizer BNT162b2 and Moderna mRNA-1273. Antibody titres did not appear to be affected by sex or geographic location. Our results identify how factors such as age and type of vaccine can influence antibody responses to vaccination, and how antibody titres wane over time. This information highlights the importance of tailoring vaccine regimens to specific populations, especially those at increased risk of severe COVID-19 and can be used to inform future vaccination strategies, scheduling of booster doses, and public health measures. [ABSTRACT FROM AUTHOR]

Simple Summary: Rabies is causing a serious threat to humans and animals almost worldwide. Immunization against the disease is important in four aspects: public health protection, animal health, economic impact, and regulatory compliance. Rabies affects a wide range of mammals, including domestic pets, livestock, and wild animals. Infected animals, usually bitten by an infected wild animal, suffer from severe neurological symptoms and eventually die. In Israel, mandatory vaccination of dogs as well as wildlife surveillance exists. When it comes to farm animals, the vaccination policy depends on a risk analysis. However, little is known regarding the optimal immunization protocol needed to protect small ruminants. To find an optimal vaccination strategy, we tested the effect of one and two doses of vaccine on sheep and goats. Initially, animals were vaccinated with one dose, and half of them received a second dose (booster) a month later. The level of antibodies was tested a month and a year later. The study demonstrated a different immune response between the different species, as one-dose vaccinated sheep showed a low maintenance of protection a year later, compared with the booster-receiving group. On the other hand, 80% of the goats which received a single dose had a sufficient antibody level a year later. Infrequent rabies cases occur in Israel, endangering humans and animals. While dogs receive mandatory vaccinations, farm animals are vaccinated voluntarily. However, optimal vaccination protocol for small ruminants is lacking. The aim of this study was to test the immunological responses to the rabies vaccine, with or without a booster, in sheep and goats; 70 ewes and 49 does participated in the trial. Following the first vaccine, 88% of the ewes and 100% of the does had a sufficient level of rabies antibodies (>0.5 IU/mL) 30 days post-vaccination. A year later, 82% of the ewes that had received a booster dose remained protected, whereas 46% of the non-boosted ewes had a sufficient antibody level. For does, 83% of those receiving a booster maintained sufficient antibody levels 1 year later; 80% of the non-boosted does remained protected, demonstrating no significant contribution of the booster dose in this group of goats. However, while the initial immunological response of the does was higher, the change in response between 1 month and 12 months post-vaccination differed significantly between species, with a greater titer reduction in the does. Differential immunological responses between individuals and between species warrant longer-term studies to recommend a proper vaccine protocol for each species. [ABSTRACT FROM AUTHOR]

Background: Understanding the facilitators, barriers and hesitancy to accepting COVID-19 booster doses is important for encouraging recommended vaccination. This evidence brief summarizes literature on the intention to accept or reject COVID-19 vaccine booster doses and the factors associated with intention/uptake among individuals in Canada. Methods: A database of COVID-19 literature established at the Public Health Agency of Canada was searched for articles referencing vaccination and knowledge, attitudes and behaviours towards COVID-19 boosters. A grey literature search of Canadian governmental and academic institutions was also conducted. Primary research conducted in Canada (n=21) and relevant systematic reviews of the global literature (n=8) were included in this evidence brief. Results: Intentions to get a booster dose in the general population have decreased between 2021--2023, with intentions varying across subpopulations. In Canada and within the global systematic reviews, facilitators, barriers and hesitancy were similar. Older age was the most common factor positively associated with intention/uptake of a booster, and the most common motivators were government/healthcare provider recommendations and helping to protect others. The main reasons for hesitancy were concerns about vaccine side effects and a lack of belief in the vaccine's efficacy. Conclusion: Intentions to get a booster dose have decreased in Canada. Understanding the reasons for vaccine hesitancy and motivators for obtaining a booster can help guide future public health COVID-19 booster vaccination programs. [ABSTRACT FROM AUTHOR]

The Delta Select channel catfish strain (DS) was developed by selection for increased growth and carcass yield. Progeny from DS and the Delta Control (DC) strain (a randomly bred strain from the same base population as DS) were compared in three trials. Trial 1: unvaccinated ~1‐year‐old fingerlings from each strain reared communally in 0.4‐ha ponds. Trial 2: vaccinated ~ 1‐year‐old fingerlings from each strain grown in separate replicated 0.4‐ha ponds and fish in about half the ponds were given an ESC vaccine‐booster at 13 months post‐hatch. Trial 3: same procedures as Trial 2, except fish were raised in replicate 0.04‐ha ponds with no vaccine‐booster. In Trial 1 DS were larger at stocking, larger at harvest, and had higher carcass yield than DC; in Trial 2 DS were larger at harvest, had better survival and higher production/ha than DC. Vaccine‐booster had no effect on fish growth or survival. DS and DC were not different for any traits in Trial 3. Although outcome varied among trials, the overall results indicated a vaccine booster did not affect growth or survival, DS strain fingerlings grew faster than DC fingerling, and DS had higher carcass yield than DC strain fish when reared communally. [ABSTRACT FROM AUTHOR]

Objectives: To assess the effect of a single clinic-based educational intervention session on parents of children aged 4.5 to 5.5 years on improving the coverage of a second booster dose of the DPT vaccine. The secondary objective was to assess the coverage of second booster dose of the DPT vaccine among children aged > 6 years and to learn about the reasons behind such dropouts, if any. Methods: The study was conducted in two phases. In the first phase, a cross-sectional study was conducted among children aged > 6 years who were attending the pediatric OPD or IPD to determine the coverage of the second booster dose of DPT vaccine and possible reasons for dropout. This was followed by a clustered randomized trial evaluating the effect of an educational intervention (clinic-based, single session) among parents of children aged 4.5 to 5.5 years for improving second DPT booster coverage. Results: A total of 384 children were enrolled in the first phase, of which 233 (60.68%) were vaccinated. Subgroup analysis showed significant differences in the vaccine coverage between children from tribal-dominant and non-tribal-dominant districts (45.10% vs 63.06%, P = 0.01). Educational intervention resulted in higher vaccination coverage (77.24%) compared to 71.43% in the control arm (P = 0.300) Conclusions: The current study showed low coverage for second booster of DPT vaccine. With educational intervention, the target immunization coverage could be attained early which has implications for reducing childhood morbidity due to vaccine-preventable diseases. [ABSTRACT FROM AUTHOR]

Bordetella pertussis infection is a highly contagious respiratory disease that can cause complications such as pneumonia and death. A total of 62,646 cases of pertussis worldwide were reported by WHO in 2022. This study aimed to obtain the pertussis seroprevalence and sociodemographic data in children aged 1–14 years and its association factors in the community based on Riskesdas 2013 and 2018. Bivariate and multivariate analysis was carried out on data from 12,753 children aged 1–14 years collected from Riskesdas 2013 and 2018 in Indonesia. Pertussis serology data was obtained based on the results of the ELISA examination which was categorized as seropositive if anti-pertussis toxin IgG ≥ 100 IU/mL or anti-pertussis IgG > 11 NTU. Pertussis seropositive indicated recent pertussis infection if no pertussis vaccine was received within the last twelve months. Pertussis seroprevalence was found at 9.8% and 33.4% in Riskesdas 2013 and 2018 respectively. While 10.1% of children aged 5–14 years were found pertussis seropositive by excluding the possible effect of vaccination in the last twelve months in Riskesdas 2013. The most important associated factor in seropositive pertussis at ages 1–4 years and 5–14 years was a history of pneumonia in the last month (OR = 2.709, 95%CI: 2.592–2.831 in Riskesdas 2013 and OR = 2.421, 95%CI: 2.299–2.550 in Riskesdas 2018). In the adjusted analysis for respondents' characteristics, low maternal education was the predictive factor that most influenced pertussis seropositivity, especially in the 2013 Riskesdas (APOR = 2.983, 95%CI: 2.670–3.333). In conclusion, the results of this study showed that the seroprevalence of pertussis was high, especially in children aged 5–14 years, so that pertussis vaccine booster administration could be considered. Because the most influencing factor towards pertussis seropositive was low maternal education, the groups of children with low-educated mothers should be targets for strengthening complete vaccination coverage and disease control. [ABSTRACT FROM AUTHOR]

Background: Decision-makers in middle-income countries need evidence on the cost-effectiveness of COVID-19 booster doses and oral antivirals to appropriately prioritise these healthcare interventions. Methods: We used a dynamic transmission model to assess the cost-effectiveness of COVID-19 booster doses and oral antivirals in Fiji, Indonesia, Papua New Guinea, and Timor-Leste. We conducted cost-effectiveness analysis from both healthcare and societal perspectives using data collated from publicly available sources. We developed an interactive R Shiny which allows the user to vary key model assumptions, such as the choice of discounting rate, and view how these assumptions affect model results. Findings: Booster doses were cost saving and therefore cost-effective in all four middle-income settings from both healthcare and societal perspectives using 3% discounting. Providing oral antivirals was cost-effective from a healthcare perspective if procured at a low generic price (US$25) or middle-income reference price (US$250); however, their cost-effectiveness was strongly influenced by rates of wastage or misuse, and the ongoing costs of care for patients hospitalised with COVID-19. The cost or wastage of rapid antigen tests did not appear strongly influential over the cost-effectiveness of oral antivirals in any of the four study settings. Conclusions: Our results support that COVID-19 booster programs are cost-effective in middle-income settings. Oral antivirals demonstrate the potential to be cost-effective if procured at or below a middle-income reference price of US$250 per schedule. Further research should quantify the rates of wastage or misuse of oral COVID-19 antivirals in middle-income settings. [ABSTRACT FROM AUTHOR]

Background: Pacific Islanders are underrepresented in vaccine efficacy trials. Few studies describe their immune response to COVID-19 vaccination. Yet, this characterization is crucial to re-enforce vaccination strategies adapted to Pacific Islanders singularities. Methods and findings: We evaluated the humoral immune response of 585 adults, self-declaring as Melanesians, Europeans, Polynesians, or belonging to other communities, to the Pfizer BNT162b2 vaccine. Anti-spike and anti-nucleoprotein IgG levels, and their capacity to neutralize SARS-CoV-2 variants and to mediate antibody-dependent cellular cytotoxicity (ADCC) were assessed across communities at 1 and 3 months post-second dose or 1 and 6 months post-third dose. All sera tested contained anti-spike antibodies and 61.3% contained anti-nucleoprotein antibodies, evidencing mostly a hybrid immunity resulting from vaccination and SARS-CoV-2 infection. At 1-month postimmunization, the 4 ethnic communities exhibited no significant differences in their anti-spike IgG levels (p value = 0.17, in an univariate linear regression model), in their capacity to mediate omicron neutralization (p value = 0.59 and 0.60, in an univariate logistic regression model at 1-month after the second and third dose, respectively) and in their capacity to mediate ADCC (p value = 0.069 in a multivariate linear regression model), regardless of the infection status. Anti-spike IgG levels and functionalities of the hybrid humoral immune response remained equivalent across the 4 ethnic communities during follow-up and at 6 months post-third dose. Conclusions: Our study evidenced Pacific Islander's robust humoral immune response to Pfizer BNT162b2 vaccine, which is pivotal to re-enforce vaccination deployment in a population at risk for severe COVID-19 (clinicaltrials.gov: NCT05135585). Trial registration: This trial has been register in ClinicalTrials.gov (ID: NCT05135585). Catherine Camille Inizan and colleagues evaluate the hybrid humoral immune response to COVID-19 infection and vaccination across a variety of Pacific Islander communities, and present data on a poorly studied population. Author summary: Why was this study done?: Pacific Islanders are at risk for severe COVID-19, in part owing to lifestyle and high rate of comorbidities. In a few studies, ethnicity had no impact on antibody levels following Pfizer BNT162b2 vaccine in Pacific Islanders; in these studies, however, follow-up was reduced and no distinction was made between the different Pacific ethnic communities. Characterizing the levels and functionality of Pacific Islanders humoral immune response to Pfizer BNT162b2 vaccine is pivotal to adapt vaccination regimens to regional singularities. What did the researchers do and find?: The current study enrolled 585 participants from New Caledonia self-declaring as Melanesians, Polynesians, Europeans, or belonging to other communities. Antibody levels and their functionality were characterized at the following time points: (1) 1 and/or 3 months after a second dose of the Pfizer BNT162b2 vaccine was administered; or (2) 1 and/or 6 months after the third dose of the vaccine. Approximately 61.3% of all sera contained traces of previous SARS-CoV-2 infection; the cohort's immune response was thus mostly hybrid, resulting from both vaccination and infection. At all time points analyzed, the hybrid humoral immune response remained equivalent across the Melanesian, Polynesian, European, and other communities: anti-spike antibody levels, which mirror the strength of the immune response, but also the capacity to mediate omicron neutralization and the capacity to mediate antibody-dependent cellular cytotoxicity (ADCC) were not significantly different across communities (p values >0.05). What do these findings mean?: The lack of community effect, despite different prevalence of obesity, suggests that SARS-CoV-2 hybrid humoral response does not differ between communities. Such robust and prototypical humoral immune response to Pfizer BNT162b2 vaccine and SARS-CoV-2 in Pacific Islanders is of prime importance to foster booster doses roll-out, with the aim to better protect this understudied population which is vulnerable to severe COVID-19. Biological confirmation of ethnicity and a larger sample size in the Polynesian community would enhance the resolution of our findings. [ABSTRACT FROM AUTHOR]