Antigen presentation dynamics shape the antibody response to variants like SARS-CoV-2 Omicron after multiple vaccinations with the original strain.

The Omicron variant of SARS-CoV-2 is not effectively neutralized by most antibodies elicited by two doses of mRNA vaccines, but a third dose increases anti-Omicron neutralizing antibodies. We reveal mechanisms underlying this observation by combining computational modeling with data from vaccinated humans. After the first dose, limited antigen availability in germinal centers (GCs) results in a response dominated by B cells that target immunodominant epitopes that are mutated in an Omicron-like variant. After the second dose, these memory cells expand and differentiate into plasma cells that secrete antibodies that are thus ineffective for such variants. However, these pre-existing antigen-specific antibodies transport antigen efficiently to secondary GCs. They also partially mask immunodominant epitopes. Enhanced antigen availability and epitope masking in secondary GCs together result in generation of memory B cells that target subdominant epitopes that are less mutated in Omicron. The third dose expands these cells and boosts anti-variant neutralizing antibodies.

Predictors of COVID-19 booster vaccine hesitancy among fully vaccinated adults in South Korea: a nationwide cross-sectional survey.

Objectives: To explore predictors of COVID-19 booster hesitancy among fully vaccinated young adults and parental factors on COVID-19 vaccine hesitancy for their children. Methods: A cross-sectional study was conducted via an online survey from December 2 to 20, 2021. We enrolled participants aged 18-49 years and elapsed ≥2 weeks after completing a primary series of COVID-19 vaccination. We estimated odds ratios (ORs) with 95% confidence intervals (CIs) using multivariate logistic regressions to evaluate factors associated with booster/vaccine hesitancy. Results: Among 2,993 participants, 48.8% indicated hesitancy (wait and see: 40.2%; definitely not: 8.7%). The booster hesitancy was more in females (OR 1.25, 95% CI 1.05-1.50), younger age group (1.44 [1.17-1.77] at 18-29 years vs. 40-49 years), lower education level (2.05 [1.10-3.82] in no high school vs. graduate degree), mRNA-1273 (2.01, 1.65-2.45 vs. BNT162b2), and those with serious adverse events following previous COVID-19 vaccination (2.03, 1.47-2.80). The main reasons for booster hesitancy were concerns about its safety (54.1%), followed by doubt about the efficacy (29.8%). Among 1,020 respondents who had children aged <18 years, 65.8% indicated COVID-19 vaccine hesitancy for their children; the hesitancy for children was higher at the younger age, and lower at lower education level, ChAdOx1 (vs. BNT162b2), and those with history of COVID-19 infection. Conclusion: Concerns on the efficacy and safety of COVID-19 vaccines were the major barrier to booster hesitancy. The initial COVID-19 vaccine type, younger age, women, lower education level, and adverse events following COVID-19 vaccine were the key predictors of booster hesitancy.

The humoral response of mRNA COVID-19 vaccine in hematological diseases: The HEMVACO study.

OBJECTIVES: The HEMVACO study evaluated the humoral response after mRNA anti-SARS-CoV-2 vaccination in an hematological cohort. METHODS: HEMVACO was a prospective, multicentric study registered in ClinicalTrials.gov, number NCT04852796. Patients received two or three doses of BNT162b2 vaccine or mRNA-1273 vaccine. The SARS-CoV-2 TrimericS IgG titers were measured 1, 3, 6 and 12 months after the second dose. RESULTS: Only 16 patients (11.6%) were naive of hematological treatment and 77 patients (55.8%) were on active treatment for hemopathy. Among the 138 analyzed patients, positive antibody titer at 1 month was obtained in 68.1% of patients with mean serology at 850±883 BAU/ml. Risk factors for vaccine failure were anti-CD20 therapy (OR=111[14.3-873]; P<0.001), hypogammaglobulinemia under 8g/L (OR=2.49[1.05-5.92]; P=0.032) and lymphopenia under 1.5G/L (OR=2.47[1.18-5.17]; P=0.015). Anti-CD20 therapy induced no anti-SARS-CoV-2 seroconversion (96%). Seventy-eight patients (56.5%) received a third dose and could reach the SARS-CoV-2 TrimericS IgG titer of high-risk patients (P=0.54). The median titer at 379 BAU/ml distinguished two groups of vaccine response (99±121 BAU/ml versus 1,109±678 BAU/ml). CONCLUSION: Vaccination should be performed before anti-CD20 therapy if the hemopathy treatment can be delayed. Administration of the third vaccine dose was interesting for patients with suboptimal response, defined by a 379 BAU/ml titer in our study.

Viral Load Dynamics in SARS-CoV-2 Omicron Breakthrough Infections.

To determine viral dynamics in Omicron breakthrough infections, we measured severe acute respiratory syndrome coronavirus 2 RNA in 206 double-vaccinated or boostered individuals. During the first 3 days following the onset of symptoms, viral loads were significantly higher (cycle threshold [Ct], 21.76) in vaccinated compared to boostered (Ct, 23.14) individuals (P = .029). However, by performing a longitudinal analysis on 32 individuals over 14 days, no difference in the viral load trajectory was observed between double-vaccinated and boostered patients. Our results indicate that booster immunization results in a reduction in detectable viral loads without significantly changing viral load dynamics over time.

A case-case study on the effect of primary and booster immunization with China-produced COVID-19 vaccines on prevention of pneumonia and viral load among vaccinated persons infected by Delta and Omicron variants.

Using a three-prefecture, two-variant COVID-19 outbreak in Henan province in January 2022, we evaluated the associations of primary and booster immunization with China-produced COVID-19 vaccines and COVID-19 pneumonia and SARS-CoV-2 viral load among persons infected by Delta or Omicron variant. We obtained demographic, clinical, vaccination, and multiple Ct values of infections ≥3 years of age. Vaccination status was either primary series ≥180 days prior to infection; primary series <180 days prior to infection, or booster dose recipient. We used logistic regression to determine odds ratios (OR) of Delta and Omicron COVID-19 pneumonia by vaccination status. We analysed minimum Ct values by vaccination status, age, and variant. Of 826 eligible cases, 405 were Delta and 421 were Omicron cases; 48.9% of Delta and 19.0% of Omicron cases had COVID-19 pneumonia. Compared with full primary vaccination ≥180 days before infection, the aOR of pneumonia was 0.48 among those completing primary vaccination <180 days and 0.18 among booster recipients among these Delta infections. Among Omicron infections, the corresponding aOR was 0.34 among those completing primary vaccination <180 days. There were too few (ten) Omicron cases among booster dose recipients to calculate a reliable OR. There were no differences in minimum Ct values by vaccination status among the 356 Delta cases or 70 Omicron cases. COVID-19 pneumonia was less common among Omicron cases than Delta cases. Full primary vaccination reduced pneumonia effectively for 6 months; boosting six months after primary vaccination resulted in further reduction. We recommend accelerating the pace of booster dose administration.

Progress in Vaccine Research Against SARS-CoV-2Variant Omicron br

By the end of2021,the Omicron mutant of SARS-CoV-2rapidly replaced the Delta mutant andbecame widely prevalent worldwide.Its S protein was mutated at36sites,resulting in significant changes invirulence and transmissibility,and was capable of immune escape.Both human and animal studies showed thatthe Omicron mutant was less virulent than the previous circulating strains.Vaccination is currently the mostcommon means of epidemic prevention and control.Studies have found that the protection of vaccines againstOmicron mutant strains has significantly decreased.Therefore,animal models are needed to evaluate theeffectiveness of new immunization strategies or specific/polyvalent vaccines against Omicron.Animalexperiments showed that booster immunization can prevent Omicron infection to a certain extent,which is one ofthe important directions to explore the immunization strategy against Omicron mutant.Besides,protective effectsof specific and polyvalent vaccines have also been preliminarily confirmed,and subsequent preclinical trials areprogressing.The development of polyvalent vaccines against existing and potential mutant strains is of greatsignificance for epidemic prevention and control.In laboratory conditions,using animal model to carry out livevirus attack experiment is a key technical means to verify the effectiveness of protective neutralizing antibody andvaccinein vivo.This article will review the research progress of vaccine against Omicron variant strain from thedirection of animal model

Measles, Mumps, and Rubella Booster Immunization Practices

Reported cases of mumps infection in the United States (U.S.) have dropped since the introduction of the single-component mumps vaccine in 1967. After introduction of the multi-component measles, mumps, rubella (MMR) vaccine, cases in the U.S. and worldwide fell to the point where the International Task Force for Disease Eradication identified mumps for eventual global eradication. By 1991, all military recruits received an MMR vaccine. By 2010, the Department of Defense (DoD) had adopted a policy of immunizing recruits with MMR vaccine only if their antibody titers to measles or rubella had dropped below threshold levels established by the commercial testing laboratories as indicative of immunity. As part of a 2010 Defense Health Board (DHB) review of MMR immunization practices by the Department of the Navy, the DHB recommended that the Navy continue the practice of MMR immunization based on serosurveillance, but that universal MMR vaccination be re-instituted in the event of an increased risk of a mumps outbreak.

Evaluation of Immunogenicity by Pseudovirus Neutralization Assays for SARS-CoV-2 Variants after Primary and Booster Immunization.

OBJECTIVES: To determine the status of immune responses after primary and booster immunization for SARS-CoV-2 variants and evaluate the differences in disease resistance based upon titers of neutralizing antibodies (NAbs) against the variants. METHODS: Participants aged 18-59 years received 2 doses of inactivated COVID-19 vaccine, 14 days apart, and a booster dose after 12 months. Blood samples were collected before vaccination (baseline), 1 and 6 months after primary immunization, and at multiple instances within 21 days of the booster dose. NAbs against the spike protein of Wuhan-Hu-1 and 3 variants were measured using pseudovirus neutralization assays. RESULTS: Of 400 enrolled participants, 387 completed visits scheduled within 6 months of the second dose and 346 participants received the booster dose in the follow-up research. After 1 month of primary immunization, geometric mean titers (GMTs) of NAbs peaked for Wuhan-Hu-1, whereas GMTs of other variants were <30. After 6 months of primary immunization, GMTs of NAbs against all strains were <30. After 3 days of booster immunization, GMTs were unaltered, seroconversion rates reached approximately 50% after 7 days, and GMTs of NAbs against all strains peaked at 14 days. CONCLUSION: Two-dose of inactivated COVID-19 vaccine induced the formation of NAbs and memory-associated immune responses, and high titers of NAbs against the variants obtained after booster immunization may further improve the effectiveness of the vaccine.

Early assessment of the safety and immunogenicity of a third dose (booster) of COVID-19 immunization in Chinese adults.

Inducing durable and effective immunity against severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) via vaccination is essential to combat the current pandemic of coronavirus disease 2019 (COVID-19). It has been noticed that the strength of anti-COVID-19 vaccination-induced immunity fades over time, which calls for an additional vaccination regime, as known as booster immunization, to restore immunity among previously vaccinated populations. Here we report a pilot open-label trial of a third dose of BBIBP-CorV, an inactivated SARS-CoV-2 vaccine (Vero cell), on 136 participants aged between 18 to 63 years. Safety and immunogenicity in terms of neutralizing antibody titers and cytokine/chemokine responses were analyzed as the main endpoint until day 28. While systemic reactogenicity was either absent or mild, SARS-CoV-2-specific neutralizing antibody titers rapidly arose in all participants within 4 weeks, surpassing the peak antibody titers elicited by the initial two-dose immunization regime. Broad increases of cellular immunity-associated cytokines and chemokines were also detected in the majority of participants after the third vaccination. Furthermore, in an exploratory study, a newly developed recombinant protein vaccine, NVSI-06-08 (CHO Cells), was found to be safe and even more effective than BBIBP-CorV in eliciting humoral immune responses in BBIBP-CorV-primed individuals. Together, these results indicate that a third immunization schedule with either homologous or heterologous vaccine showed favorable safety profiles and restored potent SARS-CoV-2-specific immunity, providing support for further trials of booster vaccination in larger populations.

COVID-19 Vaccine Booster Hesitancy (VBH) of Healthcare Workers in Czechia: National Cross-Sectional Study.

The emerging SARS-CoV-2 variants and waning vaccine-elicited immunity are two public health challenges that occurred simultaneously and synergistically during the summer of 2021 and led to a surging demand for COVID-19 vaccine booster dose (BD) rollout. This study aimed to evaluate the COVID-19 vaccine booster hesitancy (VBH) among Czech healthcare workers to explore the potential determinants of VBH. A national cross-sectional survey-based study was carried out between 3 and 11 November 2021, using an online self-administered questionnaire (SAQ) that explored the participants' demographic characteristics, COVID-19 infection and vaccine anamneses, willingness to receive COVID-19 vaccine BD, and the psychosocial drivers of VBH. A total of 3454 HCW properly responded to the online SAQ, of which 80.9% were females, 30.3% were medical professionals, and 50.5% were ≤47 years old. Most of the participants were already inoculated against SARS-CoV-2 (95.2%), and BTN162b2 was the most commonly administered vaccine (90.7%). As the study sample was planned to represent the target population, it revealed a high level of BD acceptance (71.3%) among Czech HCW, while 12.2% were still hesitant and 16.6% were against the currently available BD. These results are consistent with other recent results from central Europe. Medical professional, male, and older participants were more likely to accept BD rather than allied health professional, female, and younger participants. The BDs' perceived effectiveness against severe illness, symptomatic infection, and community transmission was a significant and strong predictor for BD acceptance, while the effectiveness against the circulating variants was not that important for our target population. The BDs' perceived safety and ethical dilemmas of vaccine justice should be addressed sufficiently while communicating with HCW and other population groups. The altruistic reasons for BD acceptance, i.e., family protection, patient protection, and community health protection, underpin the recommendation of postponing the COVID-19 vaccine mandating in favour of stressing these altruistic concerns amid public health messaging.