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Background Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are highly efficacious at preventing severe disease in the general population, current data are lacking regarding vaccine efficacy (VE) for individuals with mild immunocompromising conditions. Methods A post hoc, cross-protocol analysis of participant-level data from the blinded phase of four randomized, placebo-controlled, coronavirus disease 2019 (COVID-19) vaccine phase 3 trials (Moderna, AstraZeneca, Janssen, and Novavax) was performed. We defined a "tempered immune system" (TIS) variable via a consensus panel based on medical history and medications to determine VE against symptomatic and severe COVID-19 cases in TIS participants versus non-TIS individuals starting at 14 days after completion of the primary series through the blinded phase for each of the 4 trials. An analysis of participants living with well-controlled human immunodeficiency virus was conducted using the same methods. Results A total of 3852/30 351 (12.7%) Moderna participants, 3088/29 868 (10.3%) Novavax participants, 3549/32 380 (11.0%) AstraZeneca participants, and 5047/43 788 (11.5%) Janssen participants were identified as having a TIS. Most TIS conditions (73.9%) were due to metabolism and nutritional disorders. Vaccination (vs placebo) significantly reduced the likelihood of symptomatic and severe COVID-19 for all participants for each trial. VE was not significantly different for TIS participants versus non-TIS for either symptomatic or severe COVID-19 for each trial, nor was VE significantly different in the symptomatic endpoint for participants with human immunodeficiency virus. Conclusions For individuals with mildly immunocompromising conditions, there is no evidence of differences in VE against symptomatic or severe COVID-19 compared with those with non-TIS in the 4 COVID-19 vaccine randomized controlled efficacy trials. [ABSTRACT FROM AUTHOR]

Introduction A surge of human influenza A(H7N9) cases began in 2016 in China from an antigenically distinct lineage. Data are needed about the safety and immunogenicity of 2013 and 2017 A(H7N9) inactivated influenza vaccines (IIVs) and the effects of AS03 adjuvant, prime-boost interval, and priming effects of 2013 and 2017 A(H7N9) IIVs. Methods Healthy adults (n = 180), ages 19–50 years, were enrolled into this partially blinded, randomized, multicenter phase 2 clinical trial. Participants were randomly assigned to 1 of 6 vaccination groups evaluating homologous versus heterologous prime-boost strategies with 2 different boost intervals (21 vs 120 days) and 2 dosages (3.75 or 15 μg of hemagglutinin) administered with or without AS03 adjuvant. Reactogenicity, safety, and immunogenicity measured by hemagglutination inhibition and neutralizing antibody titers were assessed. Results Two doses of A(H7N9) IIV were well tolerated, and no safety issues were identified. Although most participants had injection site and systemic reactogenicity, these symptoms were mostly mild to moderate in severity; injection site reactogenicity was greater in vaccination groups receiving adjuvant. Immune responses were greater after an adjuvanted second dose, and with a longer interval between prime and boost. The highest hemagglutination inhibition geometric mean titer (95% confidence interval) observed against the 2017 A(H7N9) strain was 133.4 (83.6–212.6) among participants who received homologous, adjuvanted 3.75 µg + AS03/2017 doses with delayed boost interval. Conclusions Administering AS03 adjuvant with the second H7N9 IIV dose and extending the boost interval to 4 months resulted in higher peak antibody responses. These observations can broadly inform strategic approaches for pandemic preparedness. Clinical Trials Registration. NCT03589807. [ABSTRACT FROM AUTHOR]

Background Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination reduces the risk and severity of coronavirus disease 2019 (COVID-19), several variables may impact the humoral response among patients undergoing hematopoietic stem cell transplantation (HSCT). Methods A retrospective chart review was conducted among SARS-CoV-2-vaccinated HSCT recipients between 2020 and 2022 at a single center in Boston, Massachusetts. Patients age ≥18 years who received doses of Pfizer, Moderna, or J&J vaccines were included. Anti-spike (S) immunoglobulin G (IgG) titer levels were measured using the Roche assay. Responders (≥0.8 U/mL) and nonresponders (<0.8 U/mL) were categorized and analyzed. Multivariable linear and logistic regression were used to estimate the correlation coefficient and odds ratio of response magnitude and status. Results Of 152 HSCT recipients, 141 (92.8%) were responders, with a median (interquartile range [IQR]) anti-S IgG titer of 2500 (107.9–2500) U/mL at a median (IQR) of 80.5 (36–153.5) days from last dose, regardless of the number of doses received. Higher quantitative titers were associated with receipt of more vaccine doses (coeff, 205.79; 95% CI, 30.10 to 381.47; P =.022), being female (coeff, 343.5; 95% CI, −682.6 to −4.4; P =.047), being younger (<65 years; coeff, 365.2; 95% CI, −711.3 to 19.1; P =.039), and not being on anti-CD20 therapy (coeff, −1163.7; 95% CI, −1717.7 to −609.7; P =.001). Being male (odds ratio [OR], 0.11; 95% CI, 0.01 to 0.93; P =.04) and being on anti-CD20 therapy (OR, 0.16; 95% CI, 0.03 to 0.70; P =.016) were associated with nonresponse. Conclusions Overall, most HSCT recipients had high SARS-CoV-2 antibody responses. More vaccine doses improved the magnitude of immune responses. Anti-S IgG monitoring may be useful for identifying attenuated vaccine-induced responses. [ABSTRACT FROM AUTHOR]

Since January 2020, there have been over 775 million confirmed cases of Covid-19 and 7 million deaths globally. Vaccinations and increased virologic exposure in the population have attenuated the nature of the clinical illness and reduced the severe outcomes associated with the early pandemic stages. However, there is ongoing global transmission of SARS-CoV-2 and evolution of variant strains, with the potential to cause more serious illness. Only limited antiviral options are available to reduce symptomatic illness and disease progression. Unlike monoclonal antibodies, which target epitopes on the viral surface, small-molecule antivirals such as those targeting the SARS-CoV-2 main protease (Mpro) are under different selective pressure and have the potential to remain active against rapidly emerging viral variants. [ABSTRACT FROM AUTHOR]

Background Patients with lymphoid malignancies are at risk for poor coronavirus disease 2019 (COVID-19)-related outcomes and have reduced vaccine-induced immune responses. Currently, a 3-dose primary regimen of mRNA vaccines is recommended in the United States for immunocompromised hosts. Methods A prospective cohort study of healthy adults (n  = 27) and patients with lymphoid malignancies (n  = 94) was conducted, with longitudinal follow-up through completion of a 2- or 3-dose primary mRNA COVID vaccine series, respectively. Humoral responses were assessed in all participants, and cellular immunity was assessed in a subset of participants. Results The rate of seroconversion (68.1% vs 100%) and the magnitude of peak anti-S immunoglobulin G (IgG) titer (median anti-S IgG = 32.4, IQR = 0.48–75.0 vs median anti-S IgG = 72.6, IQR 51.1–100.1; P  = .0202) were both significantly lower in patients with lymphoid malignancies compared to the healthy cohort. However, peak titers of patients with lymphoid malignancies who responded to vaccination were similar to healthy cohort titers (median anti-S IgG = 64.3; IQR, 23.7–161.5; P  = .7424). The third dose seroconverted 7 of 41 (17.1%) patients who were seronegative after the first 2 doses. Although most patients with lymphoid malignancies produced vaccine-induced T-cell responses in the subset studied, B-cell frequencies were low with minimal memory cell formation. Conclusions A 3-dose primary mRNA series enhanced anti-S IgG responses to titers equivalent to healthy adults in patients with lymphoid malignancies who were seropositive after the first 2 doses and seroconverted 17.1% who were seronegative after the first 2 doses. T-cell responses were present, raising the possibility that the vaccines may confer some cell-based protection even if not measurable by anti-S IgG. [ABSTRACT FROM AUTHOR]

Authorization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines for children has ushered in a new phase of the immunization campaign to address the pandemic but has been received with mixed responses from parents, children, and opinion leaders. Herein we consider perceptions and attitudes towards pediatric SARS-CoV-2 vaccines from a Food and Drug Administration (FDA) public commentary reflecting more than 63 000 comments. [ABSTRACT FROM AUTHOR]

Vaccine clinical trials have been essential to developing effective severe acute respiratory syndrome coronavirus 2 vaccines. The challenges of supply chain disruptions, infection control, study designs, and participant factors that affect trial procedures are reviewed, with specific solutions to streamline the clinical trial process. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 messenger RNA vaccine–induced humoral response and reactogenicity profile are described in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Findings showed that 75.0% (by Simoa assay) or 80.0% (by Roche assay) of the HSCT cohort had a positive antibody response on series completion, compared with 100% in the healthy cohort. [ABSTRACT FROM AUTHOR]

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins were measured in longitudinal plasma samples collected from 13 participants who received two doses of mRNA-1273 vaccine. Eleven of 13 participants showed detectable levels of SARS-CoV-2 protein as early as day 1 after first vaccine injection. Clearance of detectable SARS-CoV-2 protein correlated with production of immunoglobulin G (IgG) and immunoglobulin A (IgA). [ABSTRACT FROM AUTHOR]

Background Measles, mumps, and rubella (MMR) vaccine is a live-attenuated vaccine usually contraindicated within the first 2 years of hematopoietic cell transplant (HCT). The objective of this study was to assess the safety of MMR vaccine when administered within 2 years of HCT. Methods We conducted a retrospective review of patients who received MMR vaccination within 2 years of an autologous or allogeneic HCT, mostly in the context of the 2019 measles outbreak. Adverse reactions were collected for 42 days postvaccination, and all hospitalizations and deaths following vaccination were reviewed. Results A total of 129 patients (75 autologous and 54 allogeneic HCT) were vaccinated 300–729 days after HCT (median, 718 days), and 39 (30%) of these were vaccinated earlier than 23 months post-transplant. Ten adverse reactions in 7 patients (5%) were identified within 42 days of vaccination: 6 respiratory tract infections (3 with fever) and 1 rash. The rash was seen in a 37-year-old female who had an allogeneic HCT 542 days before vaccination. She presented with a centrifugal maculopapular rash, confirmed to be caused by the vaccine strain rubella virus. She fully recovered. No other vaccine-associated illness was identified in the cohort after a median follow-up of 676 days. Conclusions MMR vaccine appears to be well tolerated in select HCT recipients when given between 300 and 729 days after transplant. An uncomplicated case of vaccine-associated rubella illness was seen after vaccination. Assessment of potential risks and benefits of MMR vaccination given within 2 years of HCT remains important. [ABSTRACT FROM AUTHOR]

Background Human adenovirus (HAdV) infections can lead to high mortality in solid organ transplant (SOT) recipients, with rare reports of donor-derived infection. Methods Two renal transplant recipients with HAdV-11 infection who received kidneys from the same donor are described. Whole-genome sequencing (WGS) was performed. Results WGS showed 100% nucleotide sequence identity for the 2 HAdV-11 isolates. The patients presented with distinct clinical syndromes, and both were treated with brincidofovir. Conclusions Donor-derived HAdV infection is presumed to be low; however, disseminated HAdV in SOT recipients can be severe, and clinicians should be aware of the clinical course and treatment options. [ABSTRACT FROM AUTHOR]

To assess the impact of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic on seasonal respiratory viruses, absolute case counts and viral reproductive rates from 2019–2020 were compared against previous seasons. Our findings suggest that the public health measures implemented to reduce SARS-CoV-2 transmission significantly reduced the transmission of other respiratory viruses. [ABSTRACT FROM AUTHOR]

For well over 100 years, meningococcal disease due to serogroup A Neisseria meningitidis (MenA) has caused severe epidemics globally, especially in the meningitis belt of sub-Saharan Africa. The article reviews the background and identification of MenA, the global and molecular epidemiology of MenA, and the outbreaks of MenA in the African meningitis belt. The implementation (2010) of an equitable MenA polysaccharide-protein conjugate vaccine (PsA-TT, MenAfriVac) and the strategy to control MenA in sub-Saharan Africa is described. The development of a novel multi-serogroup meningococcal conjugate vaccine (NmCV-5) that includes serogroup A is highlighted. The PubMed database (1996–2019) was searched for studies relating to MenA outbreaks, vaccine, and immunization strategies; and the Neisseria PubMLST database of 1755 MenA isolates (1915–2019) was reviewed. Using strategies from the successful MenAfriVac campaign, expanded collaborative partnerships were built to develop a novel, low-cost multivalent component meningococcal vaccine that includes MenA. This vaccine promises greater sustainability and is directed toward global control of meningococcal disease in the African meningitidis belt and beyond. The new WHO global roadmap addresses the continuing problem of bacterial meningitis, including meningococcal vaccine prevention, and provides a framework for further reducing the devastation of MenA. [ABSTRACT FROM AUTHOR]

The article addresses how SARS-CoV-2 pandemic has underscored the importance of precision vaccinology as well as the application of precision medicine principles to vaccine discovery, development, and implementation. Topics include key principles of precision vaccinology includes demographic factors such as age, sex, geographic location, and individual immune status affect; and susceptibility to and severity of coronavirus disease 2019 with safety and efficacy of COVID-19 vaccines.

The immunological parameters leading to viral persistence in chronic hepatitis B (CHB) are not clearly established. We analyzed HBV-specific immunoregulatory mechanisms in HIV-infected and HIV-uninfected HBeAg+ CHB patients to determine (1) the roles of immunoregulatory pathways, (2) the effect of anti-HBV therapy on immu-noregulatory pathways, and (3) the role of immunomodulatory therapy to overcome the effect of T regulatory cells (Tregs, CD4+CD25 + FoxP3 + ) in HBV-infected individuals. A prospective, double blind, randomized, pla-cebo-controlled trial treated HBV (HIV+/-)-infected patients with adefovir 10 mg daily or placebo for 48 weeks. HBV viral load (VL), immunophenotying, and functional studies were performed at multiple time points. Sup-pression of HBV VL with adefovir leads to decreased peripheral expansion of Tregs. While declining, Tregs significantly inhibit cytokine-secreting HBV-specific CD8+ T cell responses over 48 weeks of anti-HBV adefovir therapy (p<0.05). A large proportion of these Tregs express programmed death receptor-1 (PD-1), blockade of which in vitro leads to improved cytokine-secreting HBV-specific CD8+ T cell responses, particularly in HIV/ HBV-coinfected patients ( p < 0.05). Peripheral expansion of Treg levels correlated with HBV viral load and de-creased HBV-specific CD8+ T cells. PD-1 blockade increased survival of HBV-specific CD8+ T cells, removing the inhibitory effect of PD-1+ peripheral Tregs. Hence therapies involving PD-1 blockade in combination with directly acting antivirals should be investigated to reduce the need for life-long directly acting antiviral therapy. [ABSTRACT FROM AUTHOR]

This JAMA Insights Clinical Update emphasizes the importance of flu vaccination and nonpharmacologic public health interventions as key to managing the likely impending coepidemics of influenza and COVID-19 in fall and winter 2020-2021. [ABSTRACT FROM AUTHOR]

(1) Background: The influenza virus continues to cause significant annual morbidity and mortality. The overall efficacy of seasonal influenza vaccination is suboptimal, which is partly due to host immune factors. The effects of imprinting and repeated seasonal influenza vaccination were investigated to assess for immune factors and mechanisms that impact influenza vaccine responses. (2) Methods: Twenty participants were enrolled into a prospective pilot study based on birth cohort and seasonal influenza immunization history. Immunologic parameters were assessed over a six-month period after the seasonal influenza vaccine was administered. (3) Results: There was no significant imprinting effect, as measured by hemagglutination inhibition (HAI) fold change, HAI geometric mean titer (GMT) for Day 29 or Day 180 post-vaccination and antigen- specific antibody-secreting cells (ASC) for Day 8 post-vaccination. Individuals who had minimal prior seasonal influenza vaccination had a higher magnitude ASC response and a higher HAI fold change post-vaccination than individuals who were repeatedly vaccinated. (4) Conclusions: Repeated seasonal influenza vaccination resulted in a decreased fold change of the immune response, although individuals in this cohort tended to have high HAI titers at baseline that persisted after vaccination. Imprinting effects were not observed in this cohort. These host immune factors should be considered in the development of universal influenza vaccines. ClinicalTrials.gov Identifier: NCT03686514. [ABSTRACT FROM AUTHOR]

The cellular immune responses elicited by an investigational vaccine against an emergent variant of influenza (H3N2v) are not fully understood. Twenty-five subjects, enrolled in an investigational influenza A/H3N2v vaccine study, who received two doses of vaccine 21 days apart, were included in a sub-study of cellular immune responses. H3N2v-specific plasmablasts were determined by ELISpot 8 days after each vaccine dose and H3N2v specific CD4+ T cells were quantified by intracellular cytokine and CD154 (CD40 ligand) staining before vaccination, 8 and 21 days after each vaccine dose. Results: 95% (19/20) and 96% (24/25) subjects had pre-existing H3N2v specific memory B, and T cell responses, respectively. Plasmablast responses at Day 8 after the first vaccine administration were detected against contemporary H3N2 strains and correlated with hemagglutination inhibition HAI (IgG: p = 0.018; IgA: p < 0.001) and Neut (IgG: p = 0.038; IgA: p = 0.021) titers and with memory B cell frequency at baseline (IgA: r = 0.76, p < 0.001; IgG: r = 0.74, p = 0.0001). The CD4+ T cells at Days 8 and 21 expanded after prime vaccination and this expansion correlated strongly with early post-vaccination HAI and Neut titers (p ≤ 0.002). In an adult population, the rapid serological response observed after initial H3N2v vaccination correlates with post-vaccination plasmablasts and CD4+ T cell responses. [ABSTRACT FROM AUTHOR]

Background The host immune response to influenza vaccination can be affected by prior imprinting to a specific influenza strain based on birth cohort and prior influenza vaccination history. Understanding the underlying immune mechanisms is essential to development of an improved seasonal vaccine and an effective universal influenza vaccine. Methods This is a prospective pilot study, with a total of 20 subjects in either the H3N2 cohort (N = 10, born 1968–1977) or the H1N1 cohort (N = 10, born 1948–1957). Each cohort was further stratified by subjects who have received the influenza vaccine < 2 or ≥ 3 of the past 5 years. The FDA-approved quadrivalent 2018–19 influenza vaccine (containing A(H1N1), an A/Michigan/45/2015-like virus; A(H3N2), an A/Singapore/INFIMH-16–0019/2016-like virus; B/Colorado/06/2017-like virus; and B/Phuket/3073/2013-like virus) was administered on Day 1. Demographic information included age, gender, ethnicity, and BMI. HAI titers for each component of the vaccine were obtained at baseline, 29 days post-vaccination, and 180 days post-vaccination. HAI fold-change and HAI geometric mean titers (GMT) were analyzed. Results There was no significant difference between H1N1 or H3N2 HAI fold-change in the H3N2 birth cohort (P = 0.7496) or in the H1N1 birth cohort (P = 0.8237), Figure A. Comparing HAI fold-change for the repeatedly vs. minimally vaccinated groups, there was a significant higher fold change in the minimally vaccinated group (H1N1 HAI (P = 0.002) and H3N2 HAI (P < 0.0001), Figure B). GMT was higher at baseline for the repeatedly vaccinated group (H1N1, 70; H3N2, 98; vs. H1N1, 30; H3N2, 21 for the minimally vaccinated group); however, the GMT for the minimally vaccinated group was higher at day 29 (H1N1, 172; H3N2, 184; vs. H1N1, 422; H3N2, 299 for the minimally vaccinated group; Figure C). HAI titers and analysis at day 180 post vaccination are in progress. Conclusion There was no evidence of an imprinting effect by birth cohort for HAI titer magnitudes, even when stratified by vaccination history. There was a significantly higher HAI fold change for individuals who had received minimal influenza vaccinations in the past 5 years at 29 days post-vaccination. Individuals who had repeated vaccinations in the last 5 years had higher HAI GMT at baseline. Disclosures Nadine Rouphael, MD, Merck: I conduct as Emory PI the PNEUMO MERCK study at Emory, Research Grant; Pfizer: I conduct as co-PI the RSV PFIZER study at Emory, Research Grant; Sanofi-Pasteur: I conducted as Emory PI the CDIFFENSE trial at Emory, Research Grant. [ABSTRACT FROM AUTHOR]

Background: Bacillus cereus is a ubiquitous gram-positive rod-shaped bacterium that can cause sepsis and neuroinvasive disease in patients with acute leukemia or neutropenia., Methods: A single-center retrospective review was conducted to evaluate patients with acute leukemia, positive blood or cerebrospinal fluid test results for B cereus , and abnormal neuroradiographic findings between January 2018 and October 2022. Infection control practices were observed, environmental samples obtained, a dietary case-control study completed, and whole genome sequencing performed on environmental and clinical Bacillus isolates., Results: Five patients with B cereus neuroinvasive disease were identified. All patients had acute myeloid leukemia (AML), were receiving induction chemotherapy, and were neutropenic. Neurologic involvement included subarachnoid or intraparenchymal hemorrhage or brain abscess. All patients were treated with ciprofloxacin and survived with limited or no neurologic sequelae. B cereus was identified in 7 of 61 environmental samples and 1 of 19 dietary protein samples-these were unrelated to clinical isolates via sequencing. No point source was identified. Ciprofloxacin was added to the empiric antimicrobial regimen for patients with AML and prolonged or recurrent neutropenic fevers; no new cases were identified in the ensuing year., Conclusions: B cereus is ubiquitous in the hospital environment, at times leading to clusters with unrelated isolates. Fastidious infection control practices addressing a range of possible exposures are warranted, but their efficacy is unknown and they may not be sufficient to prevent all infections. Thus, including B cereus coverage in empiric regimens for patients with AML and persistent neutropenic fever may limit the morbidity of this pathogen., Competing Interests: Potential conflicts of interest. M. K.: royalties from UpToDate. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objectives: To determine the incidence of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection among healthcare personnel (HCP) and to assess occupational risks for SARS-CoV-2 infection., Design: Prospective cohort of healthcare personnel (HCP) followed for 6 months from May through December 2020., Setting: Large academic healthcare system including 4 hospitals and affiliated clinics in Atlanta, Georgia., Participants: HCP, including those with and without direct patient-care activities, working during the coronavirus disease 2019 (COVID-19) pandemic., Methods: Incident SARS-CoV-2 infections were determined through serologic testing for SARS-CoV-2 IgG at enrollment, at 3 months, and at 6 months. HCP completed monthly surveys regarding occupational activities. Multivariable logistic regression was used to identify occupational factors that increased the risk of SARS-CoV-2 infection., Results: Of the 304 evaluable HCP that were seronegative at enrollment, 26 (9%) seroconverted for SARS-CoV-2 IgG by 6 months. Overall, 219 participants (73%) self-identified as White race, 119 (40%) were nurses, and 121 (40%) worked on inpatient medical-surgical floors. In a multivariable analysis, HCP who identified as Black race were more likely to seroconvert than HCP who identified as White (odds ratio, 4.5; 95% confidence interval, 1.3-14.2). Increased risk for SARS-CoV-2 infection was not identified for any occupational activity, including spending >50% of a typical shift at a patient's bedside, working in a COVID-19 unit, or performing or being present for aerosol-generating procedures (AGPs)., Conclusions: In our study cohort of HCP working in an academic healthcare system, <10% had evidence of SARS-CoV-2 infection over 6 months. No specific occupational activities were identified as increasing risk for SARS-CoV-2 infection.

The use of anti-spike (S) serologic assays as surrogate measurements of SARS-CoV-2 vaccine induced immunity will be an important clinical and epidemiological tool. The characteristics of a commercially available anti-S antibody assay (Roche Elecsys anti-SARS-CoV-2 S) were evaluated in a cohort of vaccine recipients. Levels were correlated with pseudotype neutralizing antibodies (NAb) across SARS-CoV-2 variants. We recruited adults receiving a two-dose series of mRNA-1273 or BNT162b2 and collected serum at scheduled intervals up to 8 months post-first vaccination. Anti-S and NAb levels were measured, and correlation was evaluated by (i) vaccine type and (ii) SARS-CoV-2 variant (wild-type, Alpha, Beta, Gamma, and three constructs Day 146*, Day 152*, and RBM-2). Forty-six mRNA vaccine recipients were enrolled. mRNA-1273 vaccine recipients had higher peak anti-S and NAb levels compared with BNT162b2 ( P  < 0.001 for anti-S levels; P  < 0.05 for NAb levels). When anti-S and NAb levels were compared, there was good correlation (all r values ≥ 0.85) in both BNT162b2 and mRNA-1273 vaccine recipients across all evaluated variants; however, these correlations were nonlinear in nature. Lower correlation was identified between anti-S and NAb for the Beta variant ( r  = 0.88) compared with the wild-type (WT) strain ( r  = 0.94). Finally, the degree of neutralizing activity at any given anti-S level was lower for each variant compared with that of the WT strain, ( P  < 0.001). Although the Roche anti-S assay correlates well with NAb levels, this association is affected by vaccine type and SARS-CoV-2 variant. These variables must be considered when interpreting anti-S levels. IMPORTANCE We evaluated anti-spike antibody concentrations in healthy mRNA vaccinated individuals and compared these concentrations to values obtained from pseudotype neutralization assays targeting SARS-CoV-2 variants of concern to determine how well anti-spike antibodies correlate with neutralizing titers, which have been used as a marker of immunity from COVID-19 infection. We found high peak anti-spike concentrations in these individuals, with significantly higher levels seen in mRNA-1273 vaccine recipients. When we compared anti-spike and pseudotype neuralization titers, we identified good correlation; however, this correlation was affected by both vaccine type and variant, illustrating the difficulty of applying a "one size fits all" approach to anti-spike result interpretation. Our results support CDC recommendations to discourage anti-spike antibody testing to assess for immunity after vaccination and cautions providers in their interpretations of these results as a surrogate of protection in COVID-vaccinated individuals.

As new public health challenges relating to COVID-19 emerge, such as variant strains, waning vaccine efficacy over time, and decreased vaccine efficacy for special populations (immunocompromised hosts), it is important to determine a correlate of protection (CoP) to allow accurate bridging studies for special populations and against variants of concern. Large-scale phase 3 clinical trials are inefficient to rapidly assess novel vaccine candidates for variant strains or special populations, because these trials are slow and costly. Defining a practical CoP will aid in efficiently conducting future assessments to further describe protection for individuals and on a population level for surveillance., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Among 353 healthcare personnel in a longitudinal cohort in 4 hospitals in Atlanta, Georgia (May-June 2020), 23 (6.5%) had severe acute respiratory coronavirus virus 2 (SARS-CoV-2) antibodies. Spending >50% of a typical shift at the bedside (OR, 3.4; 95% CI, 1.2-10.5) and black race (OR, 8.4; 95% CI, 2.7-27.4) were associated with SARS-CoV-2 seropositivity.

Global deployment of vaccines that can provide protection across several age groups is still urgently needed to end the COVID-19 pandemic, especially in low- and middle-income countries. Although vaccines against SARS-CoV-2 based on mRNA and adenoviral vector technologies have been rapidly developed, additional practical and scalable SARS-CoV-2 vaccines are required to meet global demand. Protein subunit vaccines formulated with appropriate adjuvants represent an approach to address this urgent need. The receptor binding domain (RBD) is a key target of SARS-CoV-2 neutralizing antibodies but is poorly immunogenic. We therefore compared pattern recognition receptor (PRR) agonists alone or formulated with aluminum hydroxide (AH) and benchmarked them against AS01B and AS03-like emulsion-based adjuvants for their potential to enhance RBD immunogenicity in young and aged mice. We found that an AH and CpG adjuvant formulation (AH:CpG) produced an 80-fold increase in anti-RBD neutralizing antibody titers in both age groups relative to AH alone and protected aged mice from the SARS-CoV-2 challenge. The AH:CpG-adjuvanted RBD vaccine elicited neutralizing antibodies against both wild-type SARS-CoV-2 and the B.1.351 (beta) variant at serum concentrations comparable to those induced by the licensed Pfizer-BioNTech BNT162b2 mRNA vaccine. AH:CpG induced similar cytokine and chemokine gene enrichment patterns in the draining lymph nodes of both young adult and aged mice and enhanced cytokine and chemokine production in human mononuclear cells of younger and older adults. These data support further development of AH:CpG-adjuvanted RBD as an affordable vaccine that may be effective across multiple age groups.

Background: Antibodies against SARS-CoV-2 can be detected by various testing platforms, but a detailed understanding of assay performance is critical. Methods: We developed and validated a simple enzyme-linked immunosorbent assay (ELISA) to detect IgG binding to the receptor-binding domain (RBD) of SARS-CoV-2, which was then applied for surveillance. ELISA results were compared to a set of complimentary serologic assays using a large panel of clinical research samples. Results: The RBD ELISA exhibited robust performance in ROC curve analysis (AUC> 0.99; Se = 89%, Sp = 99.3%). Antibodies were detected in 23/353 (6.5%) healthcare workers, 6/9 RT-PCR-confirmed mild COVID-19 cases, and 0/30 non-COVID-19 cases from an ambulatory site. RBD ELISA showed a positive correlation with neutralizing activity ( p = <0.0001, R 2 = 0.26). Conclusions: We applied a validated SARS-CoV-2-specific IgG ELISA in multiple contexts and performed orthogonal testing on samples. This study demonstrates the utility of a simple serologic assay for detecting prior SARS-CoV-2 infection, particularly as a tool for efficiently testing large numbers of samples as in population surveillance. Our work also highlights that precise understanding of SARS-CoV-2 infection and immunity at the individual level, particularly with wide availability of vaccination, may be improved by orthogonal testing and/or more complex assays such as multiplex bead assays., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sherman, Smith, Zhu, Taibl, Howard-Anderson, Landay, Pisanic, Kleinhenz, Simon, Espinoza, Edupuganti, Hammond, Rouphael, Shen, Fairley, Edupuganti, Cardona-Ospina, Rodriguez-Morales, Premkumar, Wrammert, Tarleton, Fridkin, Heaney, Scherer and Collins.)

As part of the U.S. Food and Drug Administration COVID-19 vaccine review process, public commentary was solicited offering an opportunity to reflect on vaccine attitudes that may impact the uptake of coronavirus vaccines. We identified themes in the commentary that highlighted the safety, efficacy, ethics, and trustworthiness and transparency regarding the novel mRNA COVID-19 vaccines. A "Learning Immunization System" model is proposed to optimize public, private, and academic partnerships relating to vaccine development and implementation., Competing Interests: OL is a named inventor on patents relating to anti-infectives, in vitro platforms that model human immunity, and vaccine adjuvants. He received a consulting fee from GSK in 2019. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Weitzman, Sherman and Levy.)

The last decade has witnessed tremendous progress in immunology and vaccinology, owing to several scientific and technological breakthroughs. Systems vaccinology is a field that has emerged at the forefront of vaccine research and development and provides a unique way to probe immune responses to vaccination in humans. The goals of systems vaccinology are to use systems-based approaches to define signatures that can be used to predict vaccine immunogenicity and efficacy and to delineate the molecular mechanisms driving protective immunity. The application of systems biological approaches in influenza vaccination studies has enabled the discovery of early signatures that predict immunogenicity to vaccination and yielded novel mechanistic insights about vaccine-induced immunity. Here we review the contributions of systems vaccinology to influenza vaccine development and critically examine the potential of systems vaccinology toward enabling the development of a universal influenza vaccine that provides robust and durable immunity against diverse influenza viruses., (Copyright © 2021 Cold Spring Harbor Laboratory Press; all rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic that has infected over 36 million and killed over 1 million people. Informed implementation of government public health policies depends on accurate data on SARS-CoV-2 immunity at a population scale. We hypothesized that detection of SARS-CoV-2 salivary antibodies could serve as a noninvasive alternative to serological testing for monitoring of SARS-CoV-2 infection and seropositivity at a population scale. We developed a multiplex SARS-CoV-2 antibody immunoassay based on Luminex technology that comprised 12 CoV antigens, mostly derived from SARS-CoV-2 nucleocapsid (N) and spike (S). Saliva and sera collected from confirmed coronavirus disease 2019 (COVID-19) cases and from the pre-COVID-19 era were tested for IgG, IgA, and IgM to the antigen panel. Matched saliva and serum IgG responses ( n  = 28) were significantly correlated. The salivary anti-N IgG response resulted in the highest sensitivity (100%), exhibiting a positive response in 24/24 reverse transcription-PCR (RT-PCR)-confirmed COVID-19 cases sampled at >14 days post-symptom onset (DPSO), whereas the salivary anti-receptor binding domain (RBD) IgG response yielded 100% specificity. Temporal kinetics of IgG in saliva were consistent with those observed in blood and indicated that most individuals seroconvert at around 10 DPSO. Algorithms employing a combination of the IgG responses to N and S antigens result in high diagnostic accuracy (100%) by as early as 10 DPSO. These results support the use of saliva-based antibody testing as a noninvasive and scalable alternative to blood-based antibody testing., (Copyright © 2020 American Society for Microbiology.)