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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]

Introduction Human papillomavirus (HPV) is a common sexually transmitted virus that infects over 13 million people every year. Over 80% of sexually active adults will acquire HPV at some point in their lives, which is concerning since certain high-risk strains of HPV can cause six types of cancer. Vaccination against HPV is safe and effective, but despite high vaccine efficacy, vaccination rates are low among both service members and civilians. Materials and methods We conducted a retrospective, cross-sectional study to identify the percentage of United States Military Academy (USMA) Cadets who had received at least one HPV vaccine and those who completed the vaccine series. Deidentified vaccination and demographic data were retrieved from the Defense Health Agency Military Health System Data Repository (MDR) for all Cadets who were enrolled at USMA between January 2018 and May 2022 (graduating classes of 2018-2025). To identify the population of Cadets for our study and confirm presence of "any" vaccine in the MDR, Tdap vaccination information was also retrieved. The study population was defined as any Cadet who was enrolled at USMA between January 2018 and May 2022 (graduating classes of 2018-2025) and had record of an HPV and/or Tdap vaccine in the MDR. We compared demographic information between the identified population and known demographics of the USMA population to confirm that the retrieved data were consistent with population demographics. Descriptive statistics were performed to identify demographic differences based on vaccinated and unvaccinated Cadets and to determine the percentage of Cadets who received at least one HPV vaccine. Vaccine series completion was defined as the receipt of three HPV vaccine doses among those who reported receiving at least one dose of HPV vaccine or two doses if vaccinated before the age 15. Results A total of 9,567 Cadets were assessed for eligibility with 9,433 having Tdap and/or HPV vaccine on record. Of these Cadets, 5,738/9,433 (60.8%) had received at least one HPV vaccine. Of those starting the series, 4,492 completed the two- or three-dose series for a completion rate of 47.6%. We found HPV vaccine completion rate among female Cadets (55.6%) is higher than that of male Cadets (45.2%). More Cadets from minority groups received one vaccine; however, full completion rates were similar for both the groups (48.1%). In contrast, the percentage of Cadets vaccinated against Tdap was 97.2%. Most of those vaccinated received their first vaccine between the ages of 11 and 15 (53.0%) and their final vaccine after they turned 16 (68.9%). Conclusion Though the vaccination rate among the Corps of Cadets is comparable to the public, it is still less than the 80.0% goal set by the Healthy People 2030 objective. Based on these results, we recommend that the USMA modify its policy on HPV vaccine administration to encourage more vaccine uptake. We also conclude that further studies on the rationale for avoiding the vaccine are necessary to better inform educational campaigns and mitigate stigma. [ABSTRACT FROM AUTHOR]

In this experiment the development of the various chromosomal interchanges in Sowa (Anethum graveolens L.) was accomplished with the help of Gamma irradiations. The pollen mother cells of Anethum graveolens were observed to be perfectly normal in untreated plants and displayed a regular formation of eleven bivalents at diakinesis, followed by normal separation (11:11) at anaphase I. Cytological manifestation of chromosome configurations at diakinesis and metaphase-I exhibited translocation heterozygotes by the formation of either ring or chain of chromosomes in PMCs of Sowa, particularly at higher doses of Gamma irradiation (200 Gy). The translocation lines showed discernible prevalence of rings (56.58%) over chains (43.42%). In chromosomal configuration, PMCs of Irradiated plants, shows the presence of minimum one or more quadrivalent and bivalents, besides this, some PMCs showed other configurations such as trivalents, pentavalents, hexavalent, and octavalent along with variable number of univalents. At diakinesis, stage of PMCs, 2III + 1IX + 2IV + 1II + 1I configuration was observed in maximum (12.88%) followed by 6II + 1IV + 1V + 1I (12.37%) and 1VII + 1V + 2IV + 2I (11.85%). The configuration 1X + 2IV + 2II showed the lowest (5.15%) frequency. However, a variety of anomalies such as unequal separation (34.93%), laggards (21.91%) and bridges (12.32%) were also recorded. Pollen fertility was reduced (41.21 ± 0.19%) in translocation lines as comparison to control plant (98.59 ± 0.25%). Translocation heterozygotes might be used as an initial foundation for developing aneuploids with novel gene combinations. [ABSTRACT FROM AUTHOR]

We assessed the vaccination effectiveness (VE) of a COVID-19 booster vaccine dose and the association between morbidity and absenteeism with COVID-19 booster vaccine receipt among healthcare personnel (HCP) in 2022–2023 in Greece. We followed 5752 HCP from November 14, 2022 through May 28, 2023 for episodes of absenteeism. Absenteeism for non-infectious causes, pregnancy leave, or annual leave was not recorded. Full vaccination was defined as a primary vaccination series plus one booster dose within the past six months. Multivariable regression models were used to estimate the association of full COVID-19 vaccination with the outcomes of interest. A total of 1029 episodes of absenteeism occurred during the study period (17.9 episodes per 100 HCP). The mean duration of absence per episode was 5.2 days, and the total duration of absence was 5237 days. COVID-19 was diagnosed in 736 (12.8 %) HCP, asymptomatic SARS-CoV-2 infection in 62 (1.1 %) HCP, and influenza in 95 (1.7 %) HCP. Overall, COVID-19, influenza, and asymptomatic SARS-CoV-2 infection accounted for 71.5 %, 9.2 %, and 6.0 % of episodes of absenteeism, respectively. Multivariable regression models indicated that fully vaccinated HCP were absent from work for shorter periods [adjusted odds ratio (aOR): 0.42; 95 % confidence interval (CI): 0.21–0.83], were less likely to develop COVID-19 [aOR: 0.37; 95 % CI: 0.17–0.81)], and were more likely to develop an asymptomatic SARS-CoV-2 infection (aOR: 5.90; 95 % CI: 1.27–27.45). The adjusted full VE against COVID-19 was 62.8 % (95 % CI: 18.6 %-83.0 %). COVID-19 remains a significant cause of morbidity and absenteeism among HCP. Full COVID-19 vaccination status conferred significant protection against COVID-19 and was associated with shorter periods of absence from work. [ABSTRACT FROM AUTHOR]

Cotton is one of the world's most important natural fiber and cash crops. The research carried out studies of plants F1-F4 considering the importance of cytogenetic analysis of interspecific hybrids for identifying structural differences between homologous chromosomes of crossed forms and substitution of individual chromosomes or chromosome segments because of introgression of interspecific hybrids in cotton breeding. The article comprised a cytogenetic analysis of introgressive lines obtained through the participation of intergenomic crosses and F1-F4 cotton hybrids. The results revealed that in crossed variants of F1-F4 hybrid plants, the presence of open bivalents and univalents in PMC (pollen mother cell) showed the absence of complete conjugation in the chromosomes. It could be due to the structural differences between the homologous chromosomes in the crossed forms caused by exchanging chromosomes with alien ones. According to the tetrad analysis, the average value ranged from 95.65% F1L-158/16 × Sultan to 99.61% F1L-4747-48/16 × Sultan in F1 hybrids. Based on the tetrad analysis in 16 combinations, the meiotic index ranged from 96.76 ± 0.34 to 99.54 ± 0.19 in F2 hybrids and 96.51 ± 0.56 to 99.34 ± 0.30 in F3 hybrids, and in 17 combinations, the range was from 97.14 ± 0.29 to 98.92 ± 0.12 in F4 hybrids. It also confirmed that meiosis is preceding naturally in the remaining hybrid variants, with a decrease observed in the meiotic index. The results also increased the number of other types of gametes (Monod, dyad, triad, pentad, hexad, and polyad), negatively affecting normal gametes formation. [ABSTRACT FROM AUTHOR]

SUMMARY Cytokines are co-administrated with vaccines or co-expressed in the vaccine virus genome to improve protective efficacy by stimulating immune responses. Using glycosylphosphatidylinositol (GPI) anchoring by attachment to the target cytokine, we constructed recombinant Marek's disease virus (MDV) vaccine strain 301B/1 (v301B/1-rtg-IL-15) that expresses chicken interleukin-15 (IL-15) as the membrane-bound form at the cell surface. We evaluated the vaccine efficacy of v301B/1-rtg-IL-15 given as a bivalent Marek's disease (MD) vaccine in combination with turkey herpesvirus (HVT) against a very virulent plus MDV strain 648A challenge. The efficacy was compared with that of conventional bivalent MD vaccine, as a mixture with HVT plus parental v301B/1 or v301B/1-IL-15, which expresses a natural form of IL-15. The membrane-bound IL-15 expression did not interfere with the virus growth of recombinant v301B/1-rtg-IL-15. However, the MD incidence in birds vaccinated with v301B/1-rtg-IL-15 was higher than that of birds given the conventional bivalent MD vaccine containing parental v301B/1 virus, although the v301B/1-rtg-IL-15 vaccinated group showed increased natural killer cell activation at day 5 postvaccination, the same day as challenge. Overall, the protection of v301B/1-rtg-IL-15 was not improved from that of v301B/1 against very virulent plus MDV challenge. RESUMEN Eficacia de una vacuna contra el virus de la enfermedad de Marek cepa 301B/1 recombinante que expresa la interleucina-15 de pollo anclada a la membrana. Las citocinas se administran junto con vacunas o se co-expresan en el genoma del virus de la vacuna para mejorar la eficacia protectora mediante la estimulación de respuestas inmunitarias. Utilizando el anclaje de glicosilfosfatidilinositol (GPI) mediante unión a la citoquina objetivo, se construyó una cepa de vacuna recombinante del virus de la enfermedad de Marek (MDV) 301B/1 (v301B/1-rtg-IL-15) que expresa la interleucina-15 de pollo (IL-15) como la forma unida a la membrana en la superficie celular. Se evaluó la eficacia de la vacuna v301B/1-rtg-IL-15 administrada como vacuna bivalente en combinación con el herpesvirus del pavo (HVT) contra el desafío con un virus muy virulento cepa 648A de la enfermedad de Marek (MD). La eficacia se comparó con la de la vacuna bivalente convencional contra la enfermedad de Marek, como una mezcla con HVT más la cepa v301B/1 parental o con el virus recombinante v301B/1-IL-15, que expresa una forma natural de IL-15. La expresión de IL-15 unida a membrana no interfirió con el crecimiento del virus de v301B/1-rtg-IL-15 recombinante. Sin embargo, la incidencia de la enfermedad de Marek en aves vacunadas con v301B/1-rtg-IL-15 fue mayor que la de las aves que recibieron la vacuna de Marek bivalente convencional que contenía el virus v301B/1 parental, aunque el grupo vacunado con v301B/1-rtg-IL-15 mostró una mayor activación de las células asesinas naturales en el día 5 después de la vacunación, que fue el mismo día del desafío. En general, la protección por la vacuna v301B/1-rtg-IL-15 no mejoró con respecto a la conferida por v301B/1 contra un desafío muy virulento de la enfermedad de Marek. [ABSTRACT FROM AUTHOR]

Objectives: The emergence of new SARS-CoV-2 variants has led to the development of Omicron-targeting bivalent mRNA vaccines. It is crucial to understand how bivalent vaccines may improve antibody responses against new variants. Methods: A total of 107 participants, who had three COVID-19 WT mRNA vaccine doses, were recruited, and given either a monovalent (WT) or a bivalent mRNA vaccination (Pfizer/BioNTech Bivalent (WT and BA.4/BA.5) or Moderna Bivalent (WT and BA.1). Blood samples were taken before booster and at 28 days post-booster. Results: We found significantly lower fold change in serum binding IgA responses against BA.1, BA.5 and EG.5.1 spike in the bivalent booster group, compared with the monovalent (WT) booster group, following vaccination. However, this was only observed in individuals with prior infection. The relative fold change in serum binding IgA response was more skewed towards WT over variant (BA.1, BA.5 or EG.5.1) spike in previously infected bivalent-booster-vaccinees, as compared with previously infected monovalent-(WT)-booster-vaccinees. Conclusion: The findings suggest imprinting of antibody responses that is shaped by the first vaccination (WT spike). Previous infection also affects the boosting effect of follow-up vaccination. Studies are needed to understand how to induce a robust and long-lasting IgA immunity for protection against COVID-19 infection.

ABSTRACTEmerging SARS-CoV-2 sublineages continue to cause serious COVID-19 disease, but most individuals have not received any COVID-19 vaccine for >1 year. Assessment of long-term effectiveness of bivalent COVID-19 vaccines against circulating sublineages is important to inform the potential need for vaccination with updated vaccines. In this test-negative study at Kaiser Permanente Southern California, sequencing-confirmed BA.4/BA.5- or XBB-related SARS-CoV-2-positive cases (September 1, 2022 to June 30, 2023), were matched 1:3 to SARS-CoV-2-negative controls. We assessed mRNA-1273 bivalent relative (rVE) and absolute vaccine effectiveness (VE) compared to ≥2 or 0 doses of original monovalent vaccine, respectively. The rVE analysis included 20,966 cases and 62,898 controls. rVE (95%CI) against BA.4/BA.5 at 14–60 days and 121–180 days was 52.7% (46.9–57.8%) and 35.5% (−2.8–59.5%) for infection, and 59.3% (49.7–67.0%) and 33.2% (−28.2–68.0%) for Emergency Department/Urgent Care (ED/UC) encounters. For BA.4/BA.5-related hospitalizations, rVE was 71.3% (44.9–85.1%) and 52.0% (−1.2–77.3%) at 14–60 days and 61–120 days, respectively. rVE against XBB at 14–60 days and 121–180 days was 48.8% (33.4–60.7%) and −3.9% (−18.1–11.3%) for infection, 70.7% (52.4–82.0%) and 15.7% (−6.0–33.2%) for ED/UC encounters, and 87.9% (43.8–97.4%) and 57.1% (17.0–77.8%) for hospitalization. VE and subgroup analyses (age, immunocompromised status, previous SARS-CoV-2 infection) results were similar to rVE analyses. rVE of mRNA-1273 bivalent vaccine against BA.4/BA.5 and XBB infections, ED/UC encounters, and hospitalizations waned over time. Periodic revaccination with vaccines targeting emerging variants may be important in reducing COVID-19 morbidity and mortality.

ABSTRACTWe sought in-depth understanding on the evolution of factors influencing COVID-19 booster dose and bivalent vaccine hesitancy in a longitudinal semi-structured interview-based qualitative study. Serial interviews were conducted between July 25th and September 1st, 2022 (Phase I: univalent booster dose availability), and between November 21st, 2022 and January 11th, 2023 (Phase II: bivalent vaccine availability). Adults (≥18 years) in Canada who had received an initial primary series and had not received a COVID-19 booster dose were eligible for Phase I, and subsequently invited to participate in Phase II. Twenty-two of twenty-three (96%) participants completed interviews for both phases (45 interviews). Nearly half of participants identified as a woman (n = 11), the median age was 37 years (interquartile range: 32–48), and most participants were employed full-time (n = 12); no participant reported needing to vaccinate (with a primary series) for their workplace. No participant reported having received a COVID-19 booster dose at the time of their interview in Phase II. Three themes relating to the development of hesitancy toward continued vaccination against COVID-19 were identified: 1) effectiveness (frequency concerns; infection despite vaccination); 2) necessity (less threatening, low urgency, alternate protective measures); and 3) information (need for data, contradiction and confusion, lack of trust, decreased motivation). The data from interviews with individuals who had not received a COVID-19 booster dose or bivalent vaccine despite having received a primary series of COVID-19 vaccines highlights actionable targets to address vaccine hesitancy and improve public health literacy.

A global shift to bivalent mRNA vaccines is ongoing to counterbalance the diminishing effectiveness of the original monovalent vaccines due to the evolution of SARS-CoV-2 variants, yet substantial variation in the bivalent vaccine effectiveness (VE) exists across studies and a complete picture is lacking. We searched papers evaluating absolute or relative effectiveness of SARS-CoV-2 BA.1 type or BA.4/5 type bivalent mRNA vaccines on eight publication databases published from September 1st, 2022, to November 8th, 2023. Pooled VE against Omicron-associated infection and severe events (hospitalization and/or death) was estimated in reference to unvaccinated, ≥2 original monovalent doses, and ≥ 3 original monovalent doses. From 630 citations identified, 28 studies were included, involving 55,393,303 individuals. Bivalent boosters demonstrated higher effectiveness against symptomatic or any infection for all ages combined, with an absolute VE of 53.5 % (95 % CI: –22.2–82.3 %) when compared to unvaccinated and relative VE of 30.8 % (95 % CI: 22.5–38.2 %) and 28.4 % (95 % CI: 10.2–42.9 %) when compared to ≥ 2 and ≥ 3 original monovalent doses, respectively. The corresponding VE estimates for adults ≥ 60 years old were 22.5 % (95 % CI: 16.8–39.8 %), 31.4 % (95 % CI: 27.7–35.0 %), and 30.6 % (95 % CI: −13.2–57.5 %). Pooled bivalent VE estimates against severe events were higher, 72.9 % (95 % CI: 60.5–82.4 %), 57.6 % (95 % CI: 42.4–68.8 %), and 62.1 % (95 % CI: 54.6–68.3 %) for all ages, and 72.0 % (95 % CI: 51.4–83.9 %), 63.4 % (95 % CI: 41.0–77.3 %), and 60.7 % (95 % CI: 52.4–67.6 %) for adults ≥ 60 years old, compared to unvaccinated, ≥2 original monovalent doses, and ≥ 3 original monovalent doses, respectively. The bivalent boosters demonstrated superior protection against severe outcomes than the original monovalent boosters across age groups, highlighting the critical need for improving vaccine coverage, especially among the vulnerable older subpopulation. [ABSTRACT FROM AUTHOR]

• Protection from COVID-19 remains important, particularly for healthcare personnel. • Healthcare personnel in 22 U.S. states were enrolled in a case-control study. • Overall, a bivalent mRNA dose conferred 34% protection against COVID-19. • Effectiveness was similar by subgroup, but waned from 55% to 22% after two months. • Up-to-date vaccination is recommended to optimize protection against COVID-19. Bivalent mRNA vaccines were recommended since September 2022. However, coverage with a recent vaccine dose has been limited, and there are few robust estimates of bivalent VE against symptomatic SARS-CoV-2 infection (COVID-19). We estimated VE of a bivalent mRNA vaccine dose against COVID-19 among eligible U.S. healthcare personnel who had previously received monovalent mRNA vaccine doses. We conducted a case-control study in 22 U.S. states, and enrolled healthcare personnel with COVID-19 (case-participants) or without COVID-19 (control-participants) during September 2022–May 2023. Participants were considered eligible for a bivalent mRNA dose if they had received 2–4 monovalent (ancestral-strain) mRNA vaccine doses, and were ≥67 days after the most recent vaccine dose. We estimated VE of a bivalent mRNA dose using conditional logistic regression, accounting for matching by region and four-week calendar period. We adjusted estimates for age group, sex, race and ethnicity, educational level, underlying health conditions, community COVID-19 exposure, prior SARS-CoV-2 infection, and days since the last monovalent mRNA dose. Among 3,647 healthcare personnel, 1,528 were included as case-participants and 2,119 as control-participants. Participants received their last monovalent mRNA dose a median of 404 days previously; 1,234 (33.8%) also received a bivalent mRNA dose a median of 93 days previously. Overall, VE of a bivalent dose was 34.1% (95% CI, 22.6%–43.9%) against COVID-19 and was similar by product, days since last monovalent dose, number of prior doses, age group, and presence of underlying health conditions. However, VE declined from 54.8% (95% CI, 40.7%–65.6%) after 7–59 days to 21.6% (95% CI 5.6%–34.9%) after ≥60 days. Bivalent mRNA COVID-19 vaccines initially conferred approximately 55% protection against COVID-19 among U.S. healthcare personnel. However, protection waned after two months. These findings indicate moderate initial protection against symptomatic SARS-CoV-2 infection by remaining up-to-date with COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

Background The bivalent COVID-19 mRNA boosters became available in fall 2022 and were recommended alongside the seasonal influenza vaccine. However, the immunogenicity of concurrent vs separate administration of these vaccines remains unclear. Methods Here, we analyzed antibody responses in health care workers who received the bivalent COVID-19 booster and the influenza vaccine on the same day or on different days through systems serology. Antibody-binding and functional responses were characterized at peak responses and after 6 months following vaccination. Results IgG1 and neutralization responses to SARS-CoV-2 XBB.1.5 were higher at peak and after 6 months following concurrent administration as compared with separate administration of the COVID-19 and influenza vaccines. While similar results were not observed for influenza responses, no interference was noted with concurrent administration. Conclusions These data suggest that concurrent administration of these vaccines may yield higher and more durable SARS-CoV-2 neutralizing antibody responses while maintaining responses against influenza. [ABSTRACT FROM AUTHOR]

In this cohort study conducted in Hong Kong where both bivalent and monovalent formulations of BNT162b2 were available, there were no significant differences in the mortality or hospitalization between those who received bivalent and monovalent mRNA as second boosters. Bivalent and monovalent mRNA boosters appear equally protective against clinical outcomes. [ABSTRACT FROM AUTHOR]

Background Data on the effectiveness of BA.4/5 bivalent vaccine stratified by age and prior infection are lacking. Methods This test-negative study used data from individuals ≥5 years of age testing for SARS-CoV-2 with symptoms (15 September 2022 to 31 January 2023) at a large national retail pharmacy chain. The exposure was receipt of 2–4 wild-type doses and a BNT162b2 BA.4/5 bivalent vaccine (>2 months since last wild-type dose). The outcome was a positive SARS-CoV-2 test. Absolute (vs unvaccinated) and relative (vs 2–4 wild-type doses) vaccine effectiveness (VE) were calculated as (1 − adjusted odds ratio from logistic regression) × 100. VE was stratified by age and self-reported prior infection. Results Overall, 307 885 SARS-CoV-2 tests were included (7916 aged 5–11, 16 329 aged 12–17, and 283 640 aged ≥18 years). SARS-CoV-2 positivity was 39%; 21% were unvaccinated, 70% received 2–4 wild-type doses with no bivalent vaccine, and 9% received a BNT162b2 BA.4/5 bivalent dose. At a median of 1–2 months after BNT162b2 BA.4/5 bivalent vaccination, depending on age group, absolute VE was 22%–60% and was significantly higher among those reporting prior infection (range, 55%–79%) than not (range, no protection to 50%). Relative VE was 31%–64%. Conclusions BNT162b2 BA.4/5 bivalent showed early additional protection against Omicron-related symptomatic COVID-19, with hybrid immunity offering greater protection. [ABSTRACT FROM AUTHOR]

Various vaccines have been challenged by SARS‐CoV‐2 variants. Here, we reported a yeast‐derived recombinant bivalent vaccine (Bivalent wild‐type [Wt]+De) based on the wt and Delta receptor‐binding domain (RBD). Yeast derived RBD proteins based on the wt and Delta mutant were used as the prime vaccine. It was found that, in the presence of aluminium hydroxide (Alum) and unmethylated CpG‐oligodeoxynucleotides (CpG) adjuvants, more cross‐protective immunity against SARS‐CoV‐2 prototype and variants were elicited by bivalent vaccine than monovalent wtRBD or Delta RBD. Furthermore, a heterologous boosting strategy consisting of two doses of bivalent vaccines followed by one dose adenovirus vectored vaccine exhibited cross‐neutralization capacity and specific T cell responses against Delta and Omicron (BA.1 and BA.4/5) variants in mice, superior to a homologous vaccination strategy. This study suggested that heterologous prime‐boost vaccination with yeast‐derived bivalent protein vaccine could be a potential approach to address the challenge of emerging variants. [ABSTRACT FROM AUTHOR]

We estimated the effectiveness of booster doses of monovalent and bivalent mRNA COVID-19 vaccines against Omicron-associated severe outcomes among adults aged ≥50 years in Ontario, Canada. Monovalent and bivalent mRNA COVID-19 booster doses provided similar strong initial protection against severe outcomes. Uncertainty remains around waning of protection from these vaccines. [ABSTRACT FROM AUTHOR]

Background: Females with perinatal HIV (PHIV) infection are at elevated risk for anogenital high-risk human papillomavirus (HR-HPV) infection. Limited data are available around the effect of the HPV vaccination after initiation of sexual activity among PHIV youth. This study aims to assess the impact of a bivalent HPV vaccination on the persistence of anogenital HR-HPV among sexually active female PHIV youth and matched HIV-negative controls aged 12–24 years in Thailand and Vietnam. Methods: During a 3-year study, prevalent, incident, and persistent HR-HPV infection were assessed at annual visits. A subset of participants received a bivalent HPV vaccine. Samples were taken for HPV testing from the vagina, cervix, and anus. HR-HPV persistence was defined as the detection of the same genotype(s) at any anogenital compartment over ≥ two consecutive visits. Results: Of the 93 PHIV and 99 HIV-negative female youth enrolled in this study, 25 (27%) PHIV and 22 (22%) HIV-negative youth received a HPV vaccine. Persistent infection with any HR-HPV type was significantly lower among PHIV youth who received the vaccine compared to those who did not (33% vs 61%, P = 0.02); a difference was not observed among HIV-negative youth (35% vs 50%, P = 0.82). PHIV infection (adjusted prevalence ratio [aPR] 2.31, 95% CI 1.45–3.67) and not receiving a HPV vaccine (aPR, 1.19, 95%CI 1.06–1.33) were associated with persistent anogenital HR-HPV infection. Conclusions: Bivalent HPV vaccination after initiation of sexual activity was associated with reduced persistence of anogenital HR-HPV infection in Southeast Asian PHIV female youth, which may be related to vaccine cross-protection. Primary and catch-up HPV vaccinations should be prioritised for children and youth with HIV. Women living with HIV are at high risk of anogenital infection, with high-risk human papillomavirus (HPV) and associated cervical and anal cancers. In young women with perinatally acquired HIV who have experienced immune system compromise from birth, the risk of abnormal cervical cytology is even greater. We found that not receiving a HPV vaccination and having a perinatally acquired HIV were associated with persistent HPV. Catch-up HPV vaccination should be prioritised for children and youth with HIV, regardless of their sexual history. [ABSTRACT FROM AUTHOR]

Background: Long COVID has become a central public health concern. This study characterized the effectiveness of BNT162b2 BA.4/5 bivalent COVID-19 vaccine (bivalent) against long COVID symptoms. Methods: Symptomatic US adult outpatients testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023. Symptoms were assessed longitudinally using a CDC-based symptom questionnaire at Week 4, Month 3, and Month 6 following infection. The odds ratio (OR) of long COVID between vaccination groups was assessed by using mixed-effects logistic models, adjusting for multiple covariates. Results: At Week 4, among 505 participants, 260 (51%) were vaccinated with bivalent and 245 (49%) were unvaccinated. Mean age was 46.3 years, 70.7% were female, 25.1% had ≥1 comorbidity, 43.0% prior infection, 23.0% reported Nirmatrelvir/Ritonavir use. At Month 6, the bivalent cohort had 41% lower risk of long COVID with ≥3 symptoms (OR: 0.59, 95% CI, 0.36–0.96, p = 0.034) and 37% lower risk of ≥2 symptoms (OR: 0.63, 95% CI, 0.41–0.96, p = 0.030). The bivalent cohort reported fewer and less durable symptoms throughout the six-month follow-up, driven by neurologic and general symptoms, especially fatigue. Conclusions: Compared with unvaccinated participants, participants vaccinated with the bivalent were associated with approximately 40% lower risk of long COVID and less symptom burden over the six-month study duration. [ABSTRACT FROM AUTHOR]

Bivalency is a prevalent natural mechanism to enhance receptor avidity. Various two‐domain disulfide‐rich peptides exhibiting bivalent action have been identified from animal venoms. A unique characteristic of these peptides is that they induce a pharmacological response different from that provoked by any of the constituent domains. The enhanced potency and avidity of such peptides is therefore a consequence of their domain fusion by a peptide linker. The role of the linker itself, beyond conjugation, remains unclear. Here, we investigate how the linker affects the bivalency of the capsaicin receptor (TRPV1) agonist DkTx. We recombinantly produced isotope labelled DkTx using a protein splicing approach, to solve the high‐resolution solution structure of DkTx, revealing residual linker order stabilised by linker‐domain interactions leading to biased domain orientations. The significance of this was studied using a combination of mutagenesis, spin relaxation studies and electrophysiology measurements. Our results reveal that disrupting the pre‐organisation of the domains of DkTx is accompanied by reductions in potency and onset of avidity. Our findings support a model of pre‐configured two‐domain binding, in favour of the previously suggested sequential binding model. This highlights the significance of ordered elements in linker design and the natural evolution of these in bivalent toxins. [ABSTRACT FROM AUTHOR]

Protein kinase casein kinase 2 (CK2/CSNK2) is a pleiotropic kinase involved in many cellular processes and, accordingly, has been identified as a potential target for therapeutic intervention for multiple indications. Significant research effort has been invested into identifying CK2 inhibitors as potential drug candidates and potent and selective CK2 chemical probes to interrogate CK2 function. Here, we review the small molecule inhibitors reported for CK2 and discuss various orthosteric, allosteric, and bivalent inhibitors of CK2. We focus on the pyrazolo[1,5-a]pyrimidines and naphthyridines, two chemotypes that have been extensively explored for chemical probe development. We highlight the uptake and demonstrated utility of the pyrazolo[1,5-a]pyrimidine chemical probe SGC-CK2-1 by the scientific community in cellular studies. Finally, we propose criteria for an ideal in vivo chemical probe for investigating CK2 function in a living organism. While no compound currently meets these metrics, we discuss ongoing and future directions in the development of in vivo chemical probes for CK2. [ABSTRACT FROM AUTHOR]

Background: The infection status of healthcare workers (HCWs) with coronavirus disease 2019 has become a major concern worldwide. In this study, we investigated the efficacy of the number of vaccine doses on symptoms after BA.5-adapted bivalent vaccination in HCWs. Methods: We analyzed the occupation, route of infection, symptoms, and vaccination history of all HCWs who tested positive for severe acute respiratory syndrome coronavirus 2 and worked in our hospital from November 2020 to March 2023. A logistic regression analysis was performed to examine the association between the presence of BA.5-adapted bivalent vaccination and symptoms. Results: During the observation period, 531 HCWs became infected. Of these, 72 % were women, with a median age of 30 years. Nurses accounted for 57 % of the infected cases, and many of the infection routes were from family members. We examined the relationship between symptoms in 352 HCWs infected with the Omicron BA.5* variant and the number of vaccine doses. As the number of vaccine doses increased, the rate of fever decreased, while symptoms such as a runny nose and sore throat tended to increase. The logistic regression analysis showed that the rate of fever tended to decrease (odds ratio = 0.52, 95 % confidence interval: 0.26–1.01, p = 0.056) and that of a runny nose increased (odds ratio = 3.68, 95 % confidence interval: 1.17–10.6, p = 0.018) after BA.5-adapted bivalent vaccination. Conclusion: This study shows that fever is reduced and mild symptoms are increased after BA.5-adapted bivalent vaccination in BA.5-infected HCWs. This result highlights the potential effectiveness of tailored vaccination strategies in the management of emerging COVID-19 variants.

Objectives: To compare the effectiveness of bivalent and monovalent COVID-19 vaccines throughout the 2022-2023 winter season based on real-world data. Methods: This retrospective observational matched cohort study used the national vaccination program and a surveillance dataset from the Republic of Korea, and included adults aged >18 years who received bivalent or monovalent COVID-19 vaccines between October 11, 2022, and December 17, 2022. Cox proportional hazard models were used to estimate the hazard ratio for COVID-19 infection between the groups. Results: We included 29,245 matched individuals in the bivalent and monovalent vaccine groups, respectively. The bivalent vaccine recipients showed 12.2% (95% confidence interval [CI] 6.5-17.7%) additional protection against COVID-19 infection compared with the monovalent vaccine recipients. The additional protection provided by bivalent vaccines was significantly higher among residents of long-term care facilities (39.4%, 95% CI 21.6-53.1%). Maximum additional protection was observed 3 to 4 months after completing the vaccination (17.6%, 95% CI 6.6-27.3%). Conclusion: Bivalent COVID-19 vaccines showed significantly better protection against infection than monovalent vaccines among adults during the 2022-2023 winter season. Our results highlight that immunization programs with bivalent vaccines comprising recent variants can be an effective measure to prepare for seasonal COVID-19 circulation.

The search for new, effective methods for broadening the genetic polymorphism of the original breeding material remains one of important problems of hybrid maize breeding. Globally, breeding of commercial maize varieties and hybrids is carried out using diploid genotypes, whereas tetraploid sources of initial material and wild relatives of maize are poorly involved in the breeding process. The direct heteroploid crosses between diploid and tetraploid genotypes lead to the formation of weakly fertile or completely sterile triploid hybrids, which are cytologically unstable in subsequent generations. Tetraploid maize (2n=40), as well as some wild relatives with tetraploid genome, such as Zea perennis Hitchk. (2n=40) and Tripsacum dactiloides (L.) L. (2n=72), are attractive to breeders as sources for improving economically valuable traits. The attractiveness of resynthesized diploid lines is explained by the fact that unequal crossing over between homologous chromosomes forming polyvalent associations of chromosomes, more chromosomal rearrangements occur in tetraploids than in diploid genotypes, the chromosomes of which form bivalents. Synthetic tetraploid populations of maize and its tetraploid wild relatives have great potential of variability for improving diploid maize. The authors proposed a direct method for the resynthesis of doubled haploid lines using haploid induction and an indirect method for obtaining diploid lines by heteroploid crossing and subsequent segregation of a triploid hybrid in the progeny. The method of resynthesizing the tetraploid maize genome to diploid serves as an ideal model for studying the processes of crossing over in meiosis between multivalent associations of homologous chromosomes; it is promising for obtaining diploid lines with an increased frequency of recombination between the homologous chromosomes of different genomes, combined into a common one, and can serve as a source for obtaining aneuploid series.

Evidence on the impact of COVID-19 vaccination on symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Activity Impairment (WPAI) is scarce. We analyzed associations between bivalent BA.4/5 BNT162b2 (BNT162b2) and these patient-reported outcomes (PROs). Symptomatic US adults testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023 (CT.gov NCT05160636). PROs were assessed using four questionnaires measuring symptoms, HRQoL and WPAI (a CDC-based symptom survey, PROMIS Fatigue, EQ-5D-5L, WPAI-GH), from pre-COVID to Week 4 following infection. Multivariable analysis using mixed models for repeated measures was conducted, adjusting for several covariates. The study included 643 participants: 316 vaccinated with BNT162b2 and 327 unvaccinated/not up-to-date. Mean (SD) age was 46.5 years (15.9), 71.2% were female, 44.2% reported prior infection, 25.7% had ≥1 comorbidity. The BNT162b2 cohort reported fewer acute symptoms through Week 4, especially systemic and respiratory symptoms. All PROs were adversely affected, especially at Week 1; however, at that time point, the BNT162b2 cohort reported better work performance, driven by less absenteeism, and fewer work hours lost. No significant differences were observed for HRQoL COVID-19 negatively impacted patient outcomes. Compared with unvaccinated/not up-to-date participants, those vaccinated with bivalent BA.4/5 BNT162b2 reported fewer and less persistent symptoms and improved work performance. [ABSTRACT FROM AUTHOR]

Vaccination has been a game-changer in the long battle against COVID-19. However, waning vaccine-induced immunity and the immune evasion of emerging variants create challenges. The rapid-fire development of bivalent vaccines (BVs), comprising ancestral strains and a new variant, was authorized to prevent COVID-19, but the effectiveness of the updated vaccines remains largely unclear. Electronic databases were searched to investigate the immunogenicity and reactogenicity of BVs in humans. As of March 2023, 20 trials were identified. Compared with monovalent vaccination, the induced immunogenicity against ancestral strains was similar. The BVs demonstrated approximately 33–50% higher immunogenicity values against additional variant strains. An observational cohort study showed the additional clinical effectiveness of the BVs. The adverse events were similar. In conclusion, our systematic review found that the BVs had equal immunogenicity against ancestral strains without safety concerns. Approximately 33–50% increased additional antibody titers and clinical effectiveness against additional variant strains were observed in subjects with a BV vaccine with moderate heterogeneity, especially for BA.1-containing BVs. [ABSTRACT FROM AUTHOR]

• We compared the vaccine effectiveness of bivalent and monovalent COVID-19 vaccines. • Bivalent COVID-19 vaccines offer significantly better protection. • It offered greater protection to long-term care facility residents. • Maximum additional protection was observed 3-4 months after vaccination. To compare the effectiveness of bivalent and monovalent COVID-19 vaccines throughout the 2022-2023 winter season based on real-world data. This retrospective observational matched cohort study used the national vaccination program and a surveillance dataset from the Republic of Korea, and included adults aged >18 years who received bivalent or monovalent COVID-19 vaccines between October 11, 2022, and December 17, 2022. Cox proportional hazard models were used to estimate the hazard ratio for COVID-19 infection between the groups. We included 29,245 matched individuals in the bivalent and monovalent vaccine groups, respectively. The bivalent vaccine recipients showed 12.2% (95% confidence interval [CI] 6.5-17.7%) additional protection against COVID-19 infection compared with the monovalent vaccine recipients. The additional protection provided by bivalent vaccines was significantly higher among residents of long-term care facilities (39.4%, 95% CI 21.6-53.1%). Maximum additional protection was observed 3 to 4 months after completing the vaccination (17.6%, 95% CI 6.6-27.3%). Bivalent COVID-19 vaccines showed significantly better protection against infection than monovalent vaccines among adults during the 2022-2023 winter season. Our results highlight that immunization programs with bivalent vaccines comprising recent variants can be an effective measure to prepare for seasonal COVID-19 circulation. [ABSTRACT FROM AUTHOR]

• Imaging features of axillary lymphadenopathy in the setting of ipsilateral bivalent COVID-19 vaccine booster are presented. • Resolution of the axillary lymphadenopathy was demonstrated in two cases and three cases were assessed at the outset as benign. • Radiologists will continue to encounter axillary lymphadenopathy following bivalent COVID-19 vaccines. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) pandemic is a universal emergency public health issue. A large proportion of the world's population has had several spike antigen exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and/or COVID-19 vaccinations in a relatively short-term period. Although sporadic hematopoietic adverse events after COVID-19 vaccine inoculation were reported, there is currently no sufficient evidence correlating anti-spike protein immune responses and hematopoietic adverse events of vaccinations. We reported the first case of Ph-positive B-cell acute lymphoblastic leukemia (ALL) occurring after a bivalent mRNA COVID-19 vaccine inoculation. The otherwise healthy 43-year-old female patient had a total of six spike antigen exposures in the past 1.5 years. Informative pre-vaccine tests and bone marrow study results were provided. Although the causal relationship between bivalent vaccinations and the subsequent development of Ph–positive B-cell ALL cannot be determined in the case report, we propose that anti-spike protein immune responses could be a trigger for leukemia. Clinicians must investigate the hematopoietic adverse events closely after COVID-19 vaccinations. Further pre-clinical studies to investigate the safety of bivalent mRNA COVID-19 vaccine are required. [ABSTRACT FROM AUTHOR]

Background: Long COVID has become a central public health concern. This study characterized the effectiveness of BNT162b2 BA.4/5 bivalent COVID-19 vaccine (bivalent) against long COVID symptoms. Methods: Symptomatic US adult outpatients testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023. Symptoms were assessed longitudinally using a CDC-based symptom questionnaire at Week 4, Month 3, and Month 6 following infection. The odds ratio (OR) of long COVID between vaccination groups was assessed by using mixed-effects logistic models, adjusting for multiple covariates. Results: At Week 4, among 505 participants, 260 (51%) were vaccinated with bivalent and 245 (49%) were unvaccinated. Mean age was 46.3 years, 70.7% were female, 25.1% had ≥1 comorbidity, 43.0% prior infection, 23.0% reported Nirmatrelvir/Ritonavir use. At Month 6, the bivalent cohort had 41% lower risk of long COVID with ≥3 symptoms (OR: 0.59, 95% CI, 0.36–0.96, p = 0.034) and 37% lower risk of ≥2 symptoms (OR: 0.63, 95% CI, 0.41–0.96, p = 0.030). The bivalent cohort reported fewer and less durable symptoms throughout the six-month follow-up, driven by neurologic and general symptoms, especially fatigue. Conclusions: Compared with unvaccinated participants, participants vaccinated with the bivalent were associated with approximately 40% lower risk of long COVID and less symptom burden over the six-month study duration.

Receptor avidity through multivalency is a highly sought‐after property of ligands. While readily available in nature in the form of bivalent antibodies, this property remains challenging to engineer in synthetic molecules. The discovery of several bivalent venom peptides containing two homologous and independently folded domains (in a tandem repeat arrangement) has provided a unique opportunity to better understand the underpinning design of multivalency in multimeric biomolecules, as well as how naturally occurring multivalent ligands can be identified. In previous work, we classified these molecules as a larger class termed secreted cysteine‐rich repeat‐proteins (SCREPs). Here, we present an online resource; ScrepYard, designed to assist researchers in identification of SCREP sequences of interest and to aid in characterizing this emerging class of biomolecules. Analysis of sequences within the ScrepYard reveals that two‐domain tandem repeats constitute the most abundant SCREP domain architecture, while the interdomain "linker" regions connecting the functional domains are found to be abundant in amino acids with short or polar sidechains and contain an unusually high abundance of proline residues. Finally, we demonstrate the utility of ScrepYard as a virtual screening tool for discovery of putatively multivalent peptides, by using it as a resource to identify a previously uncharacterized serine protease inhibitor and confirm its predicted activity using an enzyme assay. [ABSTRACT FROM AUTHOR]

A fourth dose of a COVID-19 vaccine has been recommended by a number of authorities due to waning immunity over time and the emergence of immune-escaping variants. Here, we evaluated the safety and immunogenicity of the bivalent BV-01-B5 or V-01D-351 or the prototype V-01 for heterologous boosting in three-dose inactivated COVID-19 vaccine (ICV) recipients, in comparison with ICV homologous boosting. One pilot study (NCT05583357) included 20 participants randomized at 1:1, either receiving V-01D-351 or CoronaVac. The other one (NCT05585567) recruited 36 participants randomized at 2:1, either receiving BV-01-B5 or V-01, respectively. BV-01-B5, V-01D-351, and V-01 were safe and well-tolerated as heterologous booster shots after three doses of ICV, with adverse reactions predominantly being mild and moderate in severity, similar to the safety profile of ICV boosters. The bivalent V-01D-351 and BV-01-B5 and prototype V-01 booster demonstrated remarkable cross-reactive immunogenicity against the prototype and multiple emerging variants of concern (VOCs), with the geometric mean ratio (versus CoronaVac) in particular being 31.3 (500 vs. 16), 12.0 (192 vs. 16) and 8.5 (136 vs.16) against BA.4/5 14 days after the booster, respectively. Taken together, the modified bivalent-formulation V-01 boosters induced robust neutralizing responses against multiple Omicron sublineages, better than V-01 and remarkably superior to ICV booster, without compromising the safety and tolerability. [ABSTRACT FROM AUTHOR]

The level of neutralizing antibodies required to confer protection against COVID-19 breakthrough infections (BIs) is unclear, and the ability to know the immune status of individuals against the rapidly changing endemic variants is limited. We assessed longitudinal serum anti-RBD antibody levels and neutralizing activities (NTs) against Omicron BA.5 and XBB.1.5 in healthcare workers following the fourth monovalent and fifth bivalent BA.4–5 vaccines. The occurrence of BIs was also followed, and pre-infection antibody levels were compared between patients who developed BI and those who did not. In addition, we collected whole blood samples on the same day as the sera and stored them on filter papers (nos. 545, 590, and 424) for up to two months, then measured their NTs using dried blood spots (DBS) eluates, and compared them with the NTs in paired sera. Pre-infection levels of NTs were lower in patients who developed BI than those who did not, but the anti-RBD antibody levels were not different between them. The NTs below 50 % using 200-fold diluted sera might be one of the indicators of high risk for COVID-19 BI. However, the NTs against XBB.1.5 at 6 months after the fifth dose of bivalent BA.4–5 vaccine were lower than this threshold in almost half of infection-naïve participants. NTs measured using DBS eluates were strongly correlated with those measured using paired sera, but the time and temperature stability varied with the type of filter paper; no. 545 filter paper was found to most suitable for NT evaluation. [ABSTRACT FROM AUTHOR]

• Immune escape of SARS-CoV-2 variants spurred the development of bivalent vaccines. • We compared antibody response following monovalent or bivalent mRNA vaccination. • While IgG responses are similar, IgA responses are lower post bivalent booster. • IgA are particularly lower in bivalent-booster-vaccinees with prior infection. • IgA are skewed towards WT in bivalent-booster-vaccinees with prior infection. The emergence of new SARS-CoV-2 variants has led to the development of Omicron-targeting bivalent mRNA vaccines. It is crucial to understand how bivalent vaccines may improve antibody responses against new variants. A total of 107 participants, who had three COVID-19 WT mRNA vaccine doses, were recruited, and given either a monovalent (WT) or a bivalent mRNA vaccination (Pfizer/BioNTech Bivalent (WT and BA.4/BA.5) or Moderna Bivalent (WT and BA.1). Blood samples were taken before booster and at 28 days post-booster. We found significantly lower fold change in serum binding IgA responses against BA.1, BA.5 and EG.5.1 spike in the bivalent booster group, compared with the monovalent (WT) booster group, following vaccination. However, this was only observed in individuals with prior infection. The relative fold change in serum binding IgA response was more skewed towards WT over variant (BA.1, BA.5 or EG.5.1) spike in previously infected bivalent-booster-vaccinees, as compared with previously infected monovalent-(WT)-booster-vaccinees. The findings suggest imprinting of antibody responses that is shaped by the first vaccination (WT spike). Previous infection also affects the boosting effect of follow-up vaccination. Studies are needed to understand how to induce a robust and long-lasting IgA immunity for protection against COVID-19 infection. [ABSTRACT FROM AUTHOR]

Evidence on the impact of COVID-19 vaccination on symptoms, Health-Related Quality of Life (HRQoL) and Work Productivity and Activity Impairment (WPAI) is scarce. We analyzed associations between bivalent BA.4/5 BNT162b2 (BNT162b2) and these patient-reported outcomes (PROs). Symptomatic US adults testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023 (CT.gov NCT05160636). PROs were assessed using four questionnaires measuring symptoms, HRQoL and WPAI (a CDC-based symptom survey, PROMIS Fatigue, EQ-5D-5L, WPAI-GH), from pre-COVID to Week 4 following infection. Multivariable analysis using mixed models for repeated measures was conducted, adjusting for several covariates. The study included 643 participants: 316 vaccinated with BNT162b2 and 327 unvaccinated/not up-to-date. Mean (SD) age was 46.5 years (15.9), 71.2% were female, 44.2% reported prior infection, 25.7% had ≥1 comorbidity. The BNT162b2 cohort reported fewer acute symptoms through Week 4, especially systemic and respiratory symptoms. All PROs were adversely affected, especially at Week 1; however, at that time point, the BNT162b2 cohort reported better work performance, driven by less absenteeism, and fewer work hours lost. No significant differences were observed for HRQoL COVID-19 negatively impacted patient outcomes. Compared with unvaccinated/not up-to-date participants, those vaccinated with bivalent BA.4/5 BNT162b2 reported fewer and less persistent symptoms and improved work performance.

Vaccination has been a game-changer in the long battle against COVID-19. However, waning vaccine-induced immunity and the immune evasion of emerging variants create challenges. The rapid-fire development of bivalent vaccines (BVs), comprising ancestral strains and a new variant, was authorized to prevent COVID-19, but the effectiveness of the updated vaccines remains largely unclear. Electronic databases were searched to investigate the immunogenicity and reactogenicity of BVs in humans. As of March 2023, 20 trials were identified. Compared with monovalent vaccination, the induced immunogenicity against ancestral strains was similar. The BVs demonstrated approximately 33–50% higher immunogenicity values against additional variant strains. An observational cohort study showed the additional clinical effectiveness of the BVs. The adverse events were similar. In conclusion, our systematic review found that the BVs had equal immunogenicity against ancestral strains without safety concerns. Approximately 33–50% increased additional antibody titers and clinical effectiveness against additional variant strains were observed in subjects with a BV vaccine with moderate heterogeneity, especially for BA.1-containing BVs.

Abstract Background During male meiosis, the Y chromosome can form perfect pairing with the X chromosome. However, it is unclear whether mammalian Female germline stem cells (FGSCs) without a Y chromosome can transdifferentiate into functional haploid spermatid-like cells (SLCs). Results We found that spermatogenesis was restarted by transplanting FGSCs into Kit w/wv mutant testes. Complete meiosis and formation of SLCs was induced in vitro by testicular cells of Kit w/wv mutant mice, cytokines and retinoic acid. Healthy offspring were produced by sperm and SLCs derived from the in vivo and in vitro transdifferentiation of FGSCs, respectively. Furthermore, high-throughput chromosome conformation capture sequencing(Hi-C-seq) and “bivalent” (H3K4me3-H3K27me3) micro chromatin immunoprecipitation sequencing (μChIP-seq) experiments showed that stimulated by retinoic acid gene 8 (STRA8)/protamine 1 (PRM1)-positive transdifferentiated germ cells (tGCs) and male germ cells (mGCs) display similar chromatin dynamics and chromatin condensation during in vitro spermatogenesis. Conclusion This study demonstrates that sperm can be produced from FGSCs without a Y chromosome. This suggests a strategy for dairy cattle breeding to produce only female offspring with a high-quality genetic background.

Bivalent ligands, including bisubstrate inhibitors, are conjugates of pharmacophores, which simultaneously target two binding sites of the biomolecule. Such structures offer attainable means for the development of compounds whose ability to bind to the biological target could be modulated by an external trigger. In the present work, two deactivatable bisubstrate inhibitors of basophilic protein kinases (PKs) were constructed by conjugating the pharmacophores via linkers that could be cleaved in response to external stimuli. The inhibitor ARC-2121 incorporated a photocleavable nitrodibenzofuran-comprising β-amino acid residue in the structure of the linker. The pharmacophores of the other deactivatable inhibitor ARC-2194 were conjugated via reduction-cleavable disulfide bond. The disassembly of the inhibitors was monitored by HPLC-MS. The affinity and inhibitory potency of the inhibitors toward cAMP-dependent PK (PKAcα) were established by an equilibrium competitive displacement assay and enzyme activity assay, respectively. The deactivatable inhibitors possessed remarkably high 1–2-picomolar affinity toward PKAcα. Irradiation of ARC-2121 with 365 nm UV radiation led to reaction products possessing a 30-fold reduced affinity. The chemical reduction of ARC-2194 resulted in the decrease of affinity of over four orders of magnitude. The deactivatable inhibitors of PKs are valuable tools for the temporal inhibition or capture of these pharmacologically important enzymes. [ABSTRACT FROM AUTHOR]

For head-to-head comparison of human papillomavirus (HPV) antibody levels induced by different vaccines, 25-year-old vaccine-naive women were given either the bivalent (n = 188) or the nonavalent HPV vaccine (n = 184). Six months after vaccination antibodies against pseudovirions from 17 different HPV types (HPV6/11/16/18/31/33/35/39/45/51/52/56/58/59/66/68/73) were measured. Antibodies against HPV16/18 were higher after bivalent HPV vaccination (mean international units [IU] 1140.1 and 170.5 for HPV16 and 18, respectively) than after nonavalent vaccination (265.1 and 22.3 IUs, respectively). The bivalent vaccine commonly induced antibodies against the nonvaccine HPV types 31/33/35/45 or 58. The nonavalent vaccine induced higher antibodies against HPV6/11/31/33/45/52/58 and 35. [ABSTRACT FROM AUTHOR]

Background: Two monovalent mRNA vaccines, available in December 2020, were demonstrated to have high efficacy against both the original SARS-CoV-2 strain and variants circulating through the summer and into the fall of 2021. In the context of the Omicron/BA.1 variant, which was predominant from late fall 2021 into winter of 2022 in the United States, and subsequent Omicron subvariants that have been predominant thereafter, vaccine effectiveness of the monovalent mRNA vaccine option is attenuated., Objectives: We aim to investigate the relative effectiveness of the bivalent booster compared to the monovalent booster against SARS-CoV-2 infection in the 60 days following administration in Shelby County, TN., Design: This observational population-based cohort study utilizes COVID-19 surveillance data to identify adults who were vaccinated with a monovalent booster dose between August 1, 2022 and August 30, 2022 or a bivalent booster dose between September 1, 2022 and September 30, 2022. Both groups were followed for COVID-19 status for 60 days from their administration date., Methods: We calculated incidence rates with 95% confidence intervals and propensity-adjusted hazard ratios with 95% confidence intervals of COVID-19 diagnosis in the 60 days following administration of the booster dose between the bivalent group and the monovalent group. Stratified analysis was conducted by age group (18-34, 35-64, and 65+ years old)., Results: The incidence of reported SARS-CoV-2 infection was substantially higher for those who received the monovalent booster, across age groups. Overall, we observed a 51% lower hazard of infection during the study period among those who received the bivalent booster, compared to the monovalent booster., Conclusion: These results support and extend prior findings that the bivalent booster dose may be more effective in preventing infection against the Omicron sub-variants of SARS-CoV-2., (© The Author(s), 2024.)

BackgroundLong-term effectiveness data on bivalent COVID-19 boosters are limited.AimWe evaluated the long-term protection of bivalent boosters against severe COVID-19 among ≥ 65-year-olds in Finland.MethodsIn this register-based cohort analysis, we compared the risk of three severe COVID-19 outcomes among ≥ 65-year-olds who received a bivalent booster (Original/Omicron BA.1 or Original/BA.4-5; exposed group) between 1/9/2022 and 31/8/2023 to those who did not (unexposed). We included individuals vaccinated with at least two monovalent COVID-19 vaccine doses before 1/9/2022 and ≥ 3 months ago. The analysis was divided into two periods: 1/9/2022-28/2/2023 (BA.5 and BQ.1.X predominating) and 1/3/2023-31/8/2023 (XBB predominating). The hazards for the outcomes between exposed and unexposed individuals were compared with Cox regression.ResultsWe included 1,191,871 individuals. From 1/9/2022 to 28/2/2023, bivalent boosters were associated with a reduced risk of hospitalisation due to COVID-19 (hazard ratio (HR): 0.45; 95% confidence interval (CI): 0.37-0.55), death due to COVID-19 (HR: 0.49; 95% CI: 0.38-0.62), and death in which COVID-19 was a contributing factor (HR: 0.40; 95% CI: 0.31-0.51) during 14-60 days since vaccination. From 1/3/2023 to 31/8/2023, bivalent boosters were associated with lower risks of all three severe COVID-19 outcomes during 61-120 days since a bivalent booster (e.g. HR: 0.53; 95% CI: 0.39-0.71 for hospitalisation due to COVID-19); thereafter no notable risk reduction was observed. No difference was found between Original/Omicron BA.1 and Original/BA.4-5 boosters.ConclusionBivalent boosters initially reduced the risk of severe COVID-19 outcomes by ca 50% among ≥ 65-year-olds, but protection waned over time. These findings help guide vaccine development and vaccination programmes.

The coronavirus disease 2019 (COVID-19) pandemic is a universal emergency public health issue. A large proportion of the world’s population has had several spike antigen exposures to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and/or COVID-19 vaccinations in a relatively short-term period. Although sporadic hematopoietic adverse events after COVID-19 vaccine inoculation were reported, there is currently no sufficient evidence correlating anti-spike protein immune responses and hematopoietic adverse events of vaccinations. We reported the first case of Ph-positive B-cell acute lymphoblastic leukemia (ALL) occurring after a bivalent mRNA COVID-19 vaccine inoculation. The otherwise healthy 43-year-old female patient had a total of six spike antigen exposures in the past 1.5 years. Informative pre-vaccine tests and bone marrow study results were provided. Although the causal relationship between bivalent vaccinations and the subsequent development of Ph–positive B-cell ALL cannot be determined in the case report, we propose that anti-spike protein immune responses could be a trigger for leukemia. Clinicians must investigate the hematopoietic adverse events closely after COVID-19 vaccinations. Further pre-clinical studies to investigate the safety of bivalent mRNA COVID-19 vaccine are required.

With the emergence and rapid spread of new pandemic variants, especially variants of concern (VOCs), the development of next-generation vaccines with broad-spectrum neutralizing activities is of great importance. In this study, SCTV01C, a clinical stage bivalent vaccine based on trimeric spike extracellular domain (S-ECD) of SARS-CoV-2 variants Alpha (B.1.1.7) and Beta (B.1.351) with a squalene-based oil-in-water adjuvant was evaluated in comparison to its two corresponding (Alpha and Beta) monovalent vaccines in mouse immunogenicity studies. The two monovalent vaccines induced potent neutralizing antibody responses against the antigen-matched variants, but drastic reductions in neutralizing antibody titers against antigen-mismatched variants were observed. In comparison, the bivalent vaccine SCTV01C induced relatively higher and broad-spectrum cross-neutralizing activities against various SARS-CoV-2 variants, including the D614G variant, VOCs (B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.1.529), variants of interest (VOIs) (C.37, B.1.621), variants under monitoring (VUMs) (B.1.526, B.1.617.1, B.1.429, C.36.3) and other variants (B.1.618, 20I/484Q). All three vaccines elicited potent Th1-biased T-cell immune responses. These results provide direct evidence that variant-based multivalent vaccines could play important roles in addressing the critical issue of reduced protective efficacy against the existing and emerging SARS-CoV-2 variants. [ABSTRACT FROM AUTHOR]

Commercial influenza virus vaccines often elicit strain-specific immune responses and have difficulties preventing illness caused by antigenically drifted viral variants. In the last 20 years, the H3N2 component of the annual vaccine has been updated nearly twice as often as the H1N1 component, and in 2019, a mismatch between the wild-type (WT) H3N2 vaccine strain and circulating H3N2 influenza strains led to a vaccine efficacy of ;9%. Modern methods of developing computationally optimized broadly reactive antigens (COBRAs) for H3N2 influenza viruses utilize current viral surveillance information to design more broadly reactive vaccine antigens. Here, 7 new recombinant hemagglutinin (rHA) H3 COBRA hemagglutinin (HA) antigens were evaluated in mice. Subsequently, two candidates, J4 and NG2, were selected for further testing in influenza-preimmune animals based on their ability to elicit broadly reactive antibodies against antigenically drifted H3N2 viral isolates. In the preimmune model, monovalent formulations of J4 and NG2 elicited broadly reactive antibodies against recently circulating H3N2 influenza viruses from 2019. Bivalent mixtures of COBRA H1 and H3 rHA, Y2 1 J4, and Y2 1 NG2 outperformed multiple WT H11H3 bivalent rHA mixtures by eliciting seroprotective antibodies against H1N1 and H3N2 isolates from 2009 to 2019. Overall, the newly generated COBRA HA antigens, namely, Y2, J4, and NG2, had the ability to induce broadly reactive antibodies in influenza-naive and preimmune animals in both monovalent and bivalent formulations, and these antigens outperformed H1 and H3 WT rHA vaccine antigens by eliciting seroprotective antibodies against panels of antigenically drifted historical H1N1 and H3N2 vaccine strains from 2009 to 2019. IMPORTANCE Standard-of-care influenza virus vaccines are composed of a mixture of antigens from different influenza viral subtypes. For the first time, lead COBRA H1 and H3 HA antigens, formulated as a bivalent vaccine, have been investigated in animals with preexisting immunity to influenza viruses. The cocktail of COBRA HA antigens elicited more broadly reactive anti-HA antibodies than those elicited by a comparator bivalent wild-type HA vaccine against H1 and H3 influenza viruses isolated between 2009 and 2019. [ABSTRACT FROM AUTHOR]

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To generate gametes, sexually reproducing organisms need to achieve a reduction in ploidy, via meiosis. Several mechanisms are set in place to ensure proper reductional chromosome segregation at the first meiotic division (MI), including chromosome remodeling during late prophase I. Chromosome remodeling after crossover formation involves changes in chromosome condensation and restructuring, resulting in a compact bivalent, with sister kinetochores oriented to opposite poles, whose structure is crucial for localized loss of cohesion and accurate chromosome segregation. Here, we review the general processes involved in late prophase I chromosome remodeling, their regulation, and the strategies devised by different organisms to produce bivalents with configurations that promote accurate segregation. [ABSTRACT FROM AUTHOR]