Booster Dose Research Articles

Decoding the paradox: Understanding Elevated Hospitalization and Reduced Mortality in SARS-CoV-2 Variants

Introduction and aim: SARS-CoV-2 outbreaks occur cyclically, aligning with winter when vitamin D levels are lowest, except after new variant outbreaks. Adequate vitamin D is crucial for robust immune function. Hypovitaminosis diminishes immune responses, increasing susceptibility to viral infections. The manuscript explores the discrepancy between increased SARS-CoV-2 hospitalizations and lower mortality. Method​: SARS-CoV-2 mutants, including Delta, BQ, and XBB Omicron lineages, developed immune evasion capabilities, reducing the effectiveness of COVID-19 vaccines and bivalent boosters. The failure of COVID-19 vaccines to prevent infections and spread to others, coupled with the immune evasion exhibited by mutant viruses, contributed to continued SARS-CoV-2 outbreaks. Interestingly, dominant new mutants, despite their increased transmissibility, have caused fewer deaths. This article scrutinizes the mentioned incongruity through an analysis of published data. Results: Achieving herd immunity and eradicating SARS-CoV-2 has proven elusive due to ongoing mutagenesis and immune evasion, leading to recurrent viral outbreaks. The failure to approve repurposed early therapies for COVID-19 by regulators, as well as misinformation and weak strategies undertaken by leading health authorities, exacerbated the situation. Repurposed agents, including vitamin D and ivermectin, have demonstrated high efficacy against SARS-CoV-2 from the beginning, and remain unaffected by mutations. Despite their cost-effectiveness and widespread availability, regulatory approval for these generic agents in COVID-19 treatment is pending. Conclusion: Regulators hesitated to approve cost-effective, repurposed generic agents primarily to safeguard the temporary approval status of COVID-19 vaccines and anti-viral agents under Emergency Use Authorization, which persists. This reluctance overlooked the opportunity to implement an integrated approach with repurposed agents alongside COVID-19 vaccines, potentially reducing hospitalizations and fatalities and preventing outbreaks; this led to the failure to eradicate SARS-CoV-2 and becoming endemic. It is imperative that regulators now reconsider approving affordable generics for SARS-CoV-2 to effectively control future viral outbreaks. Non-technical Importance (Lay Abstract) Adequate vitamin D levels significantly bolster the human immune system—deficiency compromises immune responses and increases susceptibility, particularly to viruses. While new SARS-CoV-2 mutations like Omicron are less severe, they are more infectious and adept at evading immunity from vaccines; thus, they offer a limited spectrum of protection and duration. Primary COVID-19 vaccines have reduced disease severity but have failed to prevent viral spread, contributing to outbreaks. Booster doses had little effect on the virus but caused immune paresis, thus increasing susceptibility to infections. Regulators should consider approving generic, repurposed agents like vitamin D and ivermectin as adjunct therapies to address this challenge and better prepare for future pandemics. Proactively integrating vitamin D supplementation to fortify the immune system can mitigate vital outbreaks, alleviate hospital burdens, and reduce healthcare costs.

Prediction of Prospective Mutational Landscape of SARS-CoV-2 Spike ssRNA and Evolutionary Basis of Its Host Interaction.

Booster doses are crucial against severe COVID-19, as rapid virus mutations and variant emergence prolong the pandemic crisis. The virus's quick evolution, short generation-time, and adaptive changes impact virulence and evolvability, helping predictions about variant of concerns' (VOCs') landscapes. Here, in this study, we used a new computational algorithm, to predict the mutational pattern in SARS-CoV-2 ssRNA, proteomics, structural identification, mutation stability, and functional correlation, as well as immune escape mechanisms. Interestingly, the sequence diversity of SARS Coronavirus-2 has demonstrated a predominance of G- > A and C- > U substitutions. The best validation statistics are explored here in seven homologous models of the expected mutant SARS-CoV-2 spike ssRNA and employed for hACE2 and IgG interactions. The interactome profile of SARS-CoV-2 spike with hACE2 and IgG revealed a strong correlation between phylogeny and divergence time. The systematic adaptation of SARS-CoV-2 spike ssRNA influences infectivity and immune escape. Data suggest higher propensity of Adenine rich sequence promotes MHC system avoidance, preferred by A-rich codons. Phylogenetic data revealed the evolution of SARS-CoV-2 lineages' epidemiology. Our findings may unveil processes governing the genesis of immune-resistant variants, prompting a critical reassessment of the coronavirus mutation rate and exploration of hypotheses beyond mechanical aspects.

Immediate Adverse Reaction and SARS-CoV-2 Anti-Spike Receptor Binding Domain IgG of COVID-19 Vaccines Among Health Staffs.

To contain the spread of coronavirus disease 2019 (COVID-19), several vaccines have been developed. This study is intended to elucidate the level of anti-severe acute respiratory syndrome coronavirus 2 immunoglobulin G (anti-SARS-CoV-2-IgG) antibodies for COVID-19 vaccines (Pfizer BioNTech [BNT162b2], Oxford/AstraZeneca [ChAdOx1], and Sinopharm [BBIBP-CorV]) among health staff from health facilities in Duhok province, and it explored the immediate adverse reactions of COVID-19 vaccines among participants. A longitudinal study was conducted from June 1, 2021, to June 30, 2022, and 300 participants were included through simple random sampling. The immune response 1 mo after the second dose was significantly higher than the sustained immune after 5 and 9 mo as results revealed that, in 100% of study samples who had (ChAdOx1) vaccine, their antibody titers exceeded the positivity threshold of 1 AU/m, while 96% for (BNT162b2) and 90% for (BBIBP-CorV) for the first test after 1 mo from the second dose of the COVID-19 vaccine, and these rates were reduced to 94.6% for (ChAdOx1), 97.8% for (BNT162b2), and 81.9% for (BBIBP-CorV) at 5 mo after the second dose, while simultaneously the seropositivity rates were more reduced at 9 mo to 46.5% for (ChAdOx1), 67.5% for (BNT162b2), and 9.20% for (BBIBP-CorV). In terms of adverse reactionsss, fever was reported as the most prevalent after the first dose in 58% for ChAdOx1, 43% for BNT162b2, and 23% for BBIBP-CorV, followed by muscle pain, joint pain, and shoulder pain for both doses. The implications of the findings from this study are that higher and potentially longer antibody responses can be obtained if the BNT162b2 is given as compared with the other 2 vaccines. Moreover, the booster doses of the COVID-19 vaccine are highly recommended because more than 50% of the participants either have become anti-spike protein negative or have a deficient level of anti-spike protein against COVD-19 vaccines.

Antibody Response before and after the Booster Dose of Inactivated Corona Vaccine in Antibody Deficient Patients

Patients with inborn errors of immunity (IEI) are among the high-risk groups regarding COVID-19. Receiving booster doses (third and fourth) in addition to the standard doses is recommended in these patients. This study investigated the antibody response before and after a booster dose of Sinopharm vaccine in IEI patients.
 Thirty patients (>12 years) with antibody deficiencies, referred to Imam Khomeini Hospital and Children's Medical Center in Tehran, were enrolled in this prospective cross-sectional study. All patients were fully vaccinated with the BBIBP-CorV vaccine (2 doses of Sinopharm). Initial measurements of anti-receptor-binding domain (anti-RBD) and anti-nucleocapsid (anti-N) IgG antibody responses were conducted by enzyme-linked immunosorbent assay (ELISA). Subsequently, all patients received a booster dose of the vaccine. Four to six weeks after booster injection, the levels of antibodies were re-evaluated.
 Twenty patients with common variable immunodeficiency (CVID), 7 cases with agammaglobulinemia and 3 patients with hyper IgM syndrome were studied. Anti-RBD IgG and anti-N IgG antibodies increased in all patients after the booster.
 Our results indicated the need of receiving booster doses of the COVID-19 vaccine in patients with antibody deficiencies, even for enhancing humoral immune response specially in patients with CVID.

COVID-19 Vaccination Coverage - World Health Organization African Region, 2021-2023.

With the availability of authorized COVID-19 vaccines in early 2021, vaccination became an effective tool to reduce COVID-19-associated morbidity and mortality. Initially, the World Health Organization (WHO) set an ambitious target to vaccinate 70% of the global population by mid-2022. However, in July 2022, WHO recommended that all countries, including those in the African Region, prioritize COVID-19 vaccination of high-risk groups, including older adults and health care workers, to have the greatest impact on morbidity and mortality. As of December 31, 2023, approximately 860 million doses of COVID-19 vaccine had been delivered to countries in the African Region, and 646 million doses had been administered. Cumulatively, 38% of the African Region's population had received ≥1 dose, 32% had completed a primary series, and 21% had received ≥1 booster dose. Cumulative total population coverage with ≥1 dose ranged by country from 0.3% to 89%. Coverage with the primary series among older age groups was 52% (range among countries=15%-96%); primary series coverage among health care workers was 48% (range=13%-99%). Although the COVID-19 public health emergency of international concern was declared over in May 2023, current WHO recommendations reinforce the need to vaccinate priority populations at highest risk for severe COVID-19 disease and death and build more sustainable programs by integrating COVID-19 vaccination into primary health care, strengthening immunization across the life course, and improving pandemic preparedness.

Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants.

We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection. A total of 286 adults (with or without HIV) were enrolled >4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated. No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting. Overall, in the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost. Trial Registration: The study has been registered to the South African National Clinical Trial Registry (SANCTR): DOH-27-012022-7841. The approval letter from SANCTR has been provided in the up-loaded documents.

Acceptability of COVID-19 booster vaccine in malaysia: a cross-sectional study

Despite the high efficacy and safety demonstrated in clinical trials, COVID-19 booster vaccination rates in Malaysia remain below 50% among the general public. This study explores the factors influencing public acceptance of the COVID-19 booster vaccine among the Malaysian population. The questionnaire included variables on sociodemographics, knowledge, and the Health Belief Model (HBM) constructs. Based on the Chi-squared test of contingencies, a t-test and multivariate logistic regression analysis on 411 collected responses, the findings revealed that older participants, individuals of Chinese ethnicity, and those with higher education levels and incomes were more willing to accept booster vaccinations. The analysis further identified perceived susceptibility, perceived severity and perceived barriers as significant predictors influencing booster vaccination acceptance rates. Healthcare policymakers may consider targeting interventions to diminish the obstacles associated with booster vaccinations. These intervention strategies include implementing health intervention programmes, such as public health awareness initiatives, to raise awareness of the risks and severity of COVID-19, ultimately encouraging higher uptake of booster vaccines.

Public Health Response to SARS-CoV-2 in Assisted Living Facilities in New York State: March 2020-December 2022.

Assisted living facility (ALF) residents are especially vulnerable to SARS-CoV-2 infection due to the age and comorbidities of the resident population and the social nature of these facilities. To collate all New York State Department of Health guidance and regulations to control transmission of SARS-CoV-2 infection within ALFs from March 2020 through December 2022 and to include US Food and Drug Administration COVID-19 testing and vaccine authorizations. A narrative chronological review of all New York State Department of Health guidance. Documents and associated guidance and regulations are divided into 4 sections: (1) lockdown until COVID-19 vaccine emergency use authorization; (2) COVID-19 vaccine authorization until phased reopening; (3) phased reopening, vaccination requirements, and booster vaccination; (4) the period of the bivalent booster. Controlling the spread of SARS-CoV-2 within ALFs required a multifactorial approach that included stringent infection control measures, testing, and vaccination and careful attention to the social structure and support systems within ALFs. The SARS-CoV-2 pandemic highlighted the complexity of controlling spread of an easily transmissible respiratory pathogen in assisted living communities and the need to structure infection control programs within the diverse ALFs that provide care for our aging population.

Utilizing direct and indirect information to improve the COVID-19 vaccination booster scheduling

Current global COVID-19 booster scheduling strategies mainly focus on vaccinating high-risk populations at predetermined intervals. However, these strategies overlook key data: the direct insights into individual immunity levels from active serological testing and the indirect information available either through sample-based sero-surveillance, or vital demographic, location, and epidemiological factors. Our research, employing an age-, risk-, and region-structured mathematical model of disease transmission—based on COVID-19 incidence and vaccination data from Israel between 15 May 2020 and 25 October 2021—reveals that a more comprehensive strategy integrating these elements can significantly reduce COVID-19 hospitalizations without increasing existing booster coverage. Notably, the effective use of indirect information alone can considerably decrease COVID-19 cases and hospitalizations, without the need for additional vaccine doses. This approach may also be applicable in optimizing vaccination strategies for other infectious diseases, including influenza.

Factors affecting motivation for receiving a booster dose of the COVID-19 vaccine among Japanese university students and staff: a cross-sectional questionnaire survey

Understanding the factors that influence people’s decisions regarding vaccination is essential to promote vaccination. We aimed to clarify the motivations for receiving booster vaccines. We conducted a paper-based questionnaire distributed during January–February 2022 involving students and faculty staff who received the first COVID-19 vaccination at the mass vaccination program during June–September 2021 at Keio University. A total of 1725 participants were enrolled, and all completed the survey. Among these, 64.9% reported a significant adverse event (AEs) affecting daily life after the second vaccine. “Fear of severe COVID-19 illness” (72.6%) was the most common reason for getting vaccinated, followed by “concern of infecting others” (68.4%) and “fear of COVID-19 infection itself” (68.3%). Television emerged as the most influential source of information (80%), followed by university information (50.2%) and social networking sites (42.8%). Multivariate analysis revealed “fear of severe COVID-19 illness”, “fear of COVID-19 infection itself”, and “trust in the efficacy and safety of the vaccines in general” were significantly correlated with willingness to receive paid vaccinations. The severity of AEs and source of information were not related to participants’ willingness to receive booster vaccinations. Participants with positive reasons for vaccination were more likely to accept a third dose.

COVID-19 vaccination induces distinct T-cell responses in pediatric solid organ transplant recipients and immunocompetent children

Immune responses to COVID-19 vaccination are attenuated in adult solid organ transplant recipients (SOTRs) and additional vaccine doses are recommended for this population. However, whether COVID-19 mRNA vaccine responses are limited in pediatric SOTRs (pSOTRs) compared to immunocompetent children is unknown. Due to SARS-CoV-2 evolution and mutations that evade neutralizing antibodies, T cells may provide important defense in SOTRs who mount poor humoral responses. Therefore, we assessed anti-SARS-CoV-2 IgG titers, surrogate neutralization, and spike (S)-specific T-cell responses to COVID-19 mRNA vaccines in pSOTRs and their healthy siblings (pHCs) before and after the bivalent vaccine dose. Despite immunosuppression, pSOTRs demonstrated humoral responses to both ancestral strain and Omicron subvariants following the primary ancestral strain monovalent mRNA COVID-19 series and multiple booster doses. These responses were not significantly different from those observed in pHCs and significantly higher six months after vaccination than responses in adult SOTRs two weeks post-vaccination. However, pSOTRs mounted limited S-specific CD8+ T-cell responses and qualitatively distinct CD4+ T-cell responses, primarily producing IL-2 and TNF with less IFN-γ production compared to pHCs. Bivalent vaccination enhanced humoral responses in some pSOTRs but did not shift the CD4+ T-cell responses toward increased IFN-γ production. Our findings indicate that S-specific CD4+ T cells in pSOTRs have distinct qualities with unknown protective capacity, yet vaccination produces cross-reactive antibodies not significantly different from responses in pHCs. Given altered T-cell responses, additional vaccine doses in pSOTRs to maintain high titer cross-reactive antibodies may be important in ensuring protection against SARS-CoV-2.

Self-reported side effects of COVID-19 vaccines among health professions students in India.

Studies focusing on the safety and common side effects of vaccines play a crucial role in enhancing public acceptance of vaccination. Research is scarce regarding the usage of COVID-19 vaccines and the side effects experienced by health professions students in India and other countries. This study aimed to document self-reported side effects associated with COVID-19 vaccination among medical and dental students of six medical and dental colleges and teaching hospitals in four states (Tamil Nadu, Madhya Pradesh, Gujarat, and West Bengal) of India. A cross-sectional survey using purposive sampling of medical and dental students was conducted from 26 April to 26 May 2021. Data was collected using a Google Forms questionnaire capturing information regarding receiving COVID-19 vaccines, side effects and symptoms, onset and duration of symptoms, use of treatment to alleviate symptoms, awareness of haematologic risks associated with vaccination, and side effects from previous (non-COVID-19) vaccinations. The majority (94.5%) of participants received both doses of the Covishield/AstraZeneca COVID-19 vaccine. Among participants (n=492), 45.3% (n=223) reported one or more side effects. The most frequently reported side effects were soreness of the injected arm (80.3%), tiredness (78.5%), fever (71.3%), headache (64.1%), and hypersomnia (58.7%). The two most common severe symptoms were fever (14.8%) and headache (13%). Most side effects appeared on the day of vaccination: soreness of the injection site (57%), fever (43.1%), and tiredness (42.6%). Most reported symptoms persisted for one to three days-soreness of the injection site (53%), fever (47.1%), and headache (42.6%). Logistic regression showed that women were almost 85% less likely to report side effects. The study's findings corroborate the safety of the Covishield/AstraZeneca vaccine's first dose, evidenced by the relatively minor and transient nature of the side effects. However, the study underscores the necessity for ongoing research to assess the long-term impacts of COVID-19 vaccines, especially in the context of booster doses, thereby contributing to the global understanding of vaccine safety and efficacy.

Impact of immune evasion, waning and boosting on dynamics of population mixing between a vaccinated majority and unvaccinated minority.

We previously demonstrated that when vaccines prevent infection, the dynamics of mixing between vaccinated and unvaccinated sub-populations is such that use of imperfect vaccines markedly decreases risk for vaccinated people, and for the population overall. Risks to vaccinated people accrue disproportionately from contact with unvaccinated people. In the context of the emergence of Omicron SARS-CoV-2 and evolving understanding of SARS-CoV-2 epidemiology, we updated our analysis to evaluate whether our earlier conclusions remained valid. We modified a previously published Susceptible-Infectious-Recovered (SIR) compartmental model of SARS-CoV-2 with two connected sub-populations: vaccinated and unvaccinated, with non-random mixing between groups. Our expanded model incorporates diminished vaccine efficacy for preventing infection with the emergence of Omicron SARS-CoV-2 variants, waning immunity, the impact of prior immune experience on infectivity, "hybrid" effects of infection in previously vaccinated individuals, and booster vaccination. We evaluated the dynamics of an epidemic within each subgroup and in the overall population over a 10-year time horizon. Even with vaccine efficacy as low as 20%, and in the presence of waning immunity, the incidence of COVID-19 in the vaccinated subpopulation was lower than that among the unvaccinated population across the full 10-year time horizon. The cumulative risk of infection was 3-4 fold higher among unvaccinated people than among vaccinated people, and unvaccinated people contributed to infection risk among vaccinated individuals at twice the rate that would have been expected based on the frequency of contacts. These findings were robust across a range of assumptions around the rate of waning immunity, the impact of "hybrid immunity", frequency of boosting, and the impact of prior infection on infectivity in unvaccinated people. Although the emergence of the Omicron variants of SARS-CoV-2 has diminished the protective effects of vaccination against infection with SARS-CoV-2, updating our earlier model to incorporate loss of immunity, diminished vaccine efficacy and a longer time horizon, does not qualitatively change our earlier conclusions. Vaccination against SARS-CoV-2 continues to diminish the risk of infection among vaccinated people and in the population as a whole. By contrast, the risk of infection among vaccinated people accrues disproportionately from contact with unvaccinated people.

Central Retinal Vein Occlusion in COVID-19

Abstract Central retinal vein occlusion (CRVO) secondary to severe acute respiratory syndrome coronavirus 2–induced coagulation abnormalities is rare. A 32-year-old man presented with bilateral CRVO. He had a history of retinal migraine with occasional floaters and received 2 primary and a booster dose of the BNT162b2 vaccine 7 months prior. Four months before presentation, he developed acute blurring of vision in the left eye and was diagnosed with a nonischemic CRVO with dot-blot hemorrhages. He was managed conservatively with aspirin. Three weeks later, he contracted COVID-19 and received 5 days of nirmatrelvir/ritonavir. Four weeks after his COVID infection, repeat fundoscopic evaluation demonstrated resolving hemorrhages in the left eye but a new CRVO in the right eye. Antivascular endothelial growth factor injections were deferred because of normal visual acuity. He had a normal magnetic resonance imaging of the brain and a normal bilateral carotid duplex and was planned for close follow-up with ophthalmology. COVID-19 patients presenting with visual symptoms should be screened for CRVO.

Effects of astragalus extract, levamisole and ascorbic acid on humoral immunity in chickens vaccinated with newcastle disease vaccines

This study was designed to assess the effects of Astragalus extract, levamisole and ascorbic acid on the humoral immune response of chickens vaccinated with live and inactivated ND vaccines. Sixty day-old Cobb500 broiler chicks were used for the study. At day old, the maternally derived antibodies (MDA) to ND virus was determined and the chicks were then housed in a bio-secured pen with water and feed given ad-lib. On the sixth day, the MDA decay was determined thereafter, the chicks were shared into 4 treatment groups. Group A (Astragalus extract); Group B (levamisole); Group C (ascorbic acid) and Group D (Control) of 15 chicks each. Response to ND vaccinations was determined through bleeding to obtain sera for haemagglutination inhibition test at 7 and 14 days except for the second booster with inactivated Komarov vaccine where it was done at 7, 14 and 21 days post vaccination respectively. Antibody titres in the chicks 7 days post first dose of vaccination with La Sota was high in all the treatment groups above the control with 100 % of the chicks having protective antibody titre of ≥4 log2 until day 30 when the antibody titres in all the groups dropped drastically following the second dose of live La Sota vaccination as the first booster vaccine. However, following the second booster with inactivated Komarov the antibody titres increased in all the treatment groups in comparison to the control especially in groups B and C with GMTs of 5.8 ± 0.19 log2 and 6.1 ± 0.27 log2 respectively. We observed that ascorbic acid and Levamisole may have humoral immuno-stimulating effects on vaccinated chickens through yet to be fully explored mechanism. It is recommended that ascorbic acid or levamisole could be used during vaccinations as immuno-stimulating agents to enhance humoral antibody response in vaccinated flocks.

Trends in SARS-CoV-2 seroprevalence among pregnant women attending first antenatal care visits in Zambia: A repeated cross-sectional survey, 2021-2022.

SARS-CoV-2 serosurveys help estimate the extent of transmission and guide the allocation of COVID-19 vaccines. We measured SARS-CoV-2 seroprevalence among women attending ANC clinics to assess exposure trends over time in Zambia. We conducted repeated cross-sectional SARS-CoV-2 seroprevalence surveys among pregnant women aged 15-49 years attending their first ANC visits in four districts of Zambia (two urban and two rural) during September 2021-September 2022. Serologic testing was done using a multiplex bead assay which detects IgG antibodies to the nucleocapsid protein and the spike protein receptor-binding domain (RBD). We calculated monthly SARS-CoV-2 seroprevalence by district. We also categorized seropositive results as infection alone, infection and vaccination, or vaccination alone based on anti-RBD and anti-nucleocapsid test results and self-reported COVID-19 vaccination status (vaccinated was having received ≥1 dose). Among 8,304 participants, 5,296 (63.8%) were cumulatively seropositive for SARS-CoV-2 antibodies from September 2021 through September 2022. SARS-CoV-2 seroprevalence primarily increased from September 2021 to September 2022 in three districts (Lusaka: 61.8-100.0%, Chongwe: 39.6-94.7%, Chipata: 56.5-95.0%), but in Chadiza, seroprevalence increased from 27.8% in September 2021 to 77.2% in April 2022 before gradually dropping to 56.6% in July 2022. Among 5,906 participants with a valid COVID-19 vaccination status, infection alone accounted for antibody responses in 77.7% (4,590) of participants. Most women attending ANC had evidence of prior SARS-CoV-2 infection and most SARS-CoV-2 seropositivity was infection-induced. Capturing COVID-19 vaccination status and using a multiplex bead assay with anti-nucleocapsid and anti-RBD targets facilitated distinguishing infection-induced versus vaccine-induced antibody responses during a period of increasing COVID-19 vaccine coverage in Zambia. Declining seroprevalence in Chadiza may indicate waning antibodies and a need for booster vaccines. ANC clinics have a potential role in ongoing SARS-CoV-2 serosurveillance and can continue to provide insights into SARS-CoV-2 antibody dynamics to inform near real-time public health responses.

Determinants of health as predictors for differential antibody responses following SARS-CoV-2 primary and booster vaccination in an at-risk, longitudinal cohort.

Post vaccine immunity following COVID-19 mRNA vaccination may be driven by extrinsic, or controllable and intrinsic, or inherent health factors. Thus, we investigated the effects of extrinsic and intrinsic on the peak antibody response following COVID-19 primary vaccination and on the trajectory of peak antibody magnitude and durability over time. Participants in a longitudinal cohort attended visits every 3 months for up to 2 years following enrollment. At baseline, participants provided information on their demographics, recreational behaviors, and comorbid health conditions which guided our model selection process. Blood samples were collected for serum processing and spike antibody testing at each visit. Cross-sectional and longitudinal models (linear-mixed effects models) were generated to assess the relationship between selected intrinsic and extrinsic health factors on peak antibody following vaccination and to determine the influence of these predictors on antibody over time. Following cross-sectional analysis, we observed higher peak antibody titers after primary vaccination in females, those who reported recreational drug use, younger age, and prior COVID-19 history. Following booster vaccination, females and Hispanics had higher peak titers after the 3rd and 4th doses, respectively. Longitudinal models demonstrated that Moderna mRNA-1273 recipients, females, and those previously vaccinated had increased peak titers over time. Moreover, drug users and half-dose Moderna mRNA-1273 recipients had higher peak antibody titers over time following the first booster, while no predictive factors significantly affected post-second booster antibody responses. Overall, both intrinsic and extrinsic health factors play a significant role in shaping humoral immunogenicity after initial vaccination and the first booster. The absence of predictive factors for second booster immunogenicity suggests a more robust and consistent immune response after the second booster vaccine administration.

Immune features revealed by single-cell RNA and single-cell TCR/BCR sequencing in patients with rheumatoid arthritis receiving COVID-19 booster vaccination.

Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, have profoundly affected human health. Booster COVID-19 vaccines have demonstrated significant efficacy in reducing infection and severe cases. However, the effects of booster COVID-19 vaccines on key immune cell subsets and their responses in rheumatoid arthritis (RA) are not well understood. By using single-cell RNA sequencing (scRNA-seq) combined with scTCR/BCR-seq analysis, a total of 8 major and 27 minor cell clusters were identified from paired peripheral blood mononuclear cells (PBMCs) which were collected 1 week before and 4 weeks after booster vaccination in stable RA patients. Booster vaccination only had limited impact on the composition and proportions of PBMCs cell clusters. CD8+ cytotoxic T cells (CD8+T_CTL) showed a trend toward an increase after vaccination, while naive B cells and conventional dendritic cells (cDCs) showed a trend toward a decrease. Transcriptomic changes were observed after booster vaccination, primarily involving T/B cell receptor signaling pathways, phagosome, antigen processing and presenting, and viral myocarditis pathways. Interferon (IFN) and pro-inflammatory response gene sets were slightly upregulated across most major cell subpopulations in COVID-19 booster-vaccinated RA individuals. Plasma neutralizing antibody titers significantly increased after booster COVID-19 vaccination (p = 0.037). Single-cell TCR/BCR analysis revealed increased B cell clone expansion and repertoire diversity postvaccination, with no consistent alterations in T cells. Several clonotypes of BCRs and TCRs were identified to be significantly over-represented after vaccination, such as IGHV3-15 and TRBV28. Our study provided a comprehensive single-cell atlas of the peripheral immune response and TCR/BCR immune repertoire profiles to inactivated SARS-CoV-2 booster vaccination in RA patients, which helps us to understand vaccine-induced immune responses better.

Broad-spectrum Delta-BA.2 tandem-fused heterodimer mRNA vaccine delivered by lipopolyplex.

Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continues to mutate and generates new variants with increasingly severe immune escape, urging the upgrade of COVID-19 vaccines. Here, based on a similar dimeric RBD design as our previous ZF2001 vaccine, we developed a novel broad-spectrum COVID-19 mRNA vaccine, SWIM516, with chimeric Delta-BA.2 RBD dimer delivered by lipopolyplex (LPP). Unlike the popular lipid nanoparticle (LNP), this LPP-delivered mRNA expresses only in the injection site, which avoids potential toxicity to the liver. We demonstrated the broad-spectrum humoral and cellular immunogenicity of this vaccine to Delta and Omicron sub-variants in naïve mice and as booster shots. When challenged with Delta or Omicron live virus, vaccinated hACE2 transgenic mice and rhesus macaques were both protected, displaying significantly reduced viral loads and markedly relieved pathological damages. We believe the SWIM516 vaccine qualifies as a candidate for the next-generation broad-spectrum COVID-19 vaccine.

Poor durability of the neutralizing response against XBB sublineages after a bivalent mRNA COVID-19 booster dose in persons with HIV.

We estimated the dynamics of the neutralizing response against XBB sublineages and T cell response in persons with HIV (PWH) with previous AIDS and/or CD4 < 200/mm3 receiving the bivalent original strain/BA.4-5 booster dose in fall 2022. Samples were collected before the shot (Day 0), 15 days, 3, and 6 months after. PWH were stratified by immunization status: hybrid immunity (HI; vaccination plus COVID-19) versus nonhybrid immunity (nHI; vaccination only). Fifteen days after the booster, 16% and 30% of PWH were nonresponders in terms of anti-XBB.1.16 or anti-EG.5.1 nAbs, respectively. Three months after, a significant waning of anti-XBB.1.16, EG.5.1 and -XBB.1 nAbs was observed both in HI and nHI but nAbs in HI were higher than in nHI. Six months after both HI and nHI individuals displayed low mean levels of anti-XBB.1.16 and EG.5.1 nAbs. Regarding T cell response, IFN-γ values were stable over time and similar in HI and nHI. Our data showed that in PWH, during the prevalent circulation of the XBB.1.16, EG.5.1, and other XBB sublineages, a mRNA bivalent vaccine might not confer broad protection against them. With a view to the 2023/2024 vaccination campaign, the use of the monovalent XBB.1.5 mRNA vaccine should be urgently warranted in PWH to provide adequate protection.