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1.
PLoS One ; 19(5): e0302579, 2024.
Article En | MEDLINE | ID: mdl-38722969

Since March 2020, the COVID-19 pandemic has swiftly propagated, triggering a competitive race among medical firms to forge vaccines that thwart the infection. Lebanon initiated its vaccination campaign on February 14, 2021. Despite numerous studies conducted to elucidate the characteristics of immune responses elicited by vaccination, the topic remains unclear. Here, we aimed to track the progression of anti-spike SARS-CoV-2 antibody titers at two-time points (T1: shortly after the second vaccination dose, T2: six months later) within a cohort of 201 adults who received Pfizer-BioNTech (BNT162b2), AstraZeneca, or Sputnik V vaccines in North Lebanon. Blood specimens were obtained from participants, and antibody titers against SARS-CoV-2 were quantified through the Elecsys-Anti-SARS-CoV-2 S assay (Roche Diagnostics, Switzerland). We used univariate analysis and multivariable logistic regression models to predict determinants influencing the decline in immune response and the occurrence of breakthrough infections among vaccinated patients. Among the 201 participants, 141 exhibited unchanging levels of antibody titers between the two sample collections, 55 displayed waning antibody titers, and only five participants demonstrated heightened antibody levels. Notably, age emerged as the sole variable significantly linked to the waning immune response. Moreover, the BNT162b2 vaccine exhibited significantly higher efficacy concerning the occurrence of breakthrough infections when compared with the AstraZeneca vaccine. Overall, our study reflected the immune status of a sample of vaccinated adults in North Lebanon. Further studies on a larger scale are needed at the national level to follow the immune response after vaccination, especially after the addition of the third vaccination dose.


Antibodies, Viral , COVID-19 , SARS-CoV-2 , Humans , Male , Lebanon/epidemiology , Female , Adult , COVID-19/prevention & control , COVID-19/immunology , COVID-19/epidemiology , Antibodies, Viral/blood , Antibodies, Viral/immunology , SARS-CoV-2/immunology , Middle Aged , Spike Glycoprotein, Coronavirus/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Vaccination , Aged , Young Adult , BNT162 Vaccine/immunology , Breakthrough Infections
2.
PLoS One ; 19(5): e0303244, 2024.
Article En | MEDLINE | ID: mdl-38728294

To predict protective immunity to SARS-CoV-2, cellular immunity seems to be more sensitive than humoral immunity. Through an Interferon-Gamma (IFN-γ) Release Assay (IGRA), we show that, despite a marked decrease in total antibodies, 94.3% of 123 healthcare workers have a positive cellular response 6 months after inoculation with the 2nd dose of BNT162b2 vaccine. Despite the qualitative relationship found, we did not observe a quantitative correlation between IFN-γ and IgG levels against SARS-CoV-2. Using stimulated whole blood from a subset of participants, we confirmed the specific T-cell response to SARS-CoV-2 by dosing elevated levels of the IL-6, IL-10 and TNF-α. Through a 20-month follow-up, we found that none of the infected participants had severe COVID-19 and that the first positive cases were only 12 months after the 2nd dose inoculation. Future studies are needed to understand if IGRA-SARS-CoV-2 can be a powerful diagnostic tool to predict future COVID-19 severe disease, guiding vaccination policies.


Antibodies, Viral , BNT162 Vaccine , COVID-19 , Health Personnel , Interferon-gamma Release Tests , SARS-CoV-2 , Humans , BNT162 Vaccine/immunology , COVID-19/immunology , COVID-19/prevention & control , Female , Male , SARS-CoV-2/immunology , Adult , Middle Aged , Antibodies, Viral/blood , Antibodies, Viral/immunology , Interferon-gamma/blood , Vaccination , Immunoglobulin G/blood , Immunoglobulin G/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Immunity, Cellular , Interleukin-10/blood , Interleukin-10/immunology , Interleukin-6/blood , Interleukin-6/immunology , Tumor Necrosis Factor-alpha/blood
3.
Elife ; 122024 May 08.
Article En | MEDLINE | ID: mdl-38716629

SARS-CoV-2 vaccines have been used worldwide to combat COVID-19 pandemic. To elucidate the factors that determine the longevity of spike (S)-specific antibodies, we traced the characteristics of S-specific T cell clonotypes together with their epitopes and anti-S antibody titers before and after BNT162b2 vaccination over time. T cell receptor (TCR) αß sequences and mRNA expression of the S-responded T cells were investigated using single-cell TCR- and RNA-sequencing. Highly expanded 199 TCR clonotypes upon stimulation with S peptide pools were reconstituted into a reporter T cell line for the determination of epitopes and restricting HLAs. Among them, we could determine 78 S epitopes, most of which were conserved in variants of concern (VOCs). After the 2nd vaccination, T cell clonotypes highly responsive to recall S stimulation were polarized to follicular helper T (Tfh)-like cells in donors exhibiting sustained anti-S antibody titers (designated as 'sustainers'), but not in 'decliners'. Even before vaccination, S-reactive CD4+ T cell clonotypes did exist, most of which cross-reacted with environmental or symbiotic microbes. However, these clonotypes contracted after vaccination. Conversely, S-reactive clonotypes dominated after vaccination were undetectable in pre-vaccinated T cell pool, suggesting that highly responding S-reactive T cells were established by vaccination from rare clonotypes. These results suggest that de novo acquisition of memory Tfh-like cells upon vaccination may contribute to the longevity of anti-S antibody titers.


Antibodies, Viral , BNT162 Vaccine , COVID-19 Vaccines , COVID-19 , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Vaccination , Humans , Antibodies, Viral/immunology , Antibodies, Viral/blood , Spike Glycoprotein, Coronavirus/immunology , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/prevention & control , BNT162 Vaccine/immunology , BNT162 Vaccine/administration & dosage , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Female , Male , Epitopes, T-Lymphocyte/immunology , Adult , T-Lymphocytes, Helper-Inducer/immunology , Middle Aged
4.
Health Aff (Millwood) ; 43(5): 659-665, 2024 May.
Article En | MEDLINE | ID: mdl-38709973

We investigated county-level variation in mRNA COVID-19 vaccine use among Medicare beneficiaries throughout the United States. There was greater use of Pfizer-BioNTech vaccines than Moderna vaccines in urban areas for first and booster doses.


COVID-19 Vaccines , COVID-19 , Medicare , Rural Population , Urban Population , Humans , United States , COVID-19/prevention & control , Urban Population/statistics & numerical data , Medicare/statistics & numerical data , Aged , Female , Male , BNT162 Vaccine , SARS-CoV-2
5.
JCI Insight ; 9(9)2024 May 08.
Article En | MEDLINE | ID: mdl-38716734

mRNA vaccines are likely to become widely used for the prevention of infectious diseases in the future. Nevertheless, a notable gap exists in mechanistic data, particularly concerning the potential effects of sequential mRNA immunization or preexisting immunity on the early innate immune response triggered by vaccination. In this study, healthy adults, with or without documented prior SARS-CoV-2 infection, were vaccinated with the BNT162b2/Comirnaty mRNA vaccine. Prior infection conferred significantly stronger induction of proinflammatory and type I IFN-related gene signatures, serum cytokines, and monocyte expansion after the prime vaccination. The response to the second vaccination further increased the magnitude of the early innate response in both study groups. The third vaccination did not further increase vaccine-induced inflammation. In vitro stimulation of PBMCs with TLR ligands showed no difference in cytokine responses between groups, or before or after prime vaccination, indicating absence of a trained immunity effect. We observed that levels of preexisting antigen-specific CD4 T cells, antibody, and memory B cells correlated with elements of the early innate response to the first vaccination. Our data thereby indicate that preexisting memory formed by infection may augment the innate immune activation induced by mRNA vaccines.


BNT162 Vaccine , COVID-19 Vaccines , COVID-19 , Cytokines , Immunity, Innate , SARS-CoV-2 , Vaccination , Humans , Immunity, Innate/immunology , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Adult , Male , BNT162 Vaccine/immunology , BNT162 Vaccine/administration & dosage , Female , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Vaccination/methods , Cytokines/immunology , mRNA Vaccines/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Middle Aged , CD4-Positive T-Lymphocytes/immunology , Young Adult , Vaccines, Synthetic/immunology , Vaccines, Synthetic/administration & dosage
6.
Influenza Other Respir Viruses ; 18(5): e13290, 2024 May.
Article En | MEDLINE | ID: mdl-38706402

BACKGROUND: Priming with ChAdOx1 followed by heterologous boosting is considered in several countries. Nevertheless, analyses comparing the immunogenicity of heterologous booster to homologous primary vaccination regimens and natural infection are lacking. In this study, we aimed to conduct a comparative assessment of the immunogenicity between homologous primary vaccination regimens and heterologous prime-boost vaccination using BNT162b2 or mRNA-1273. METHODS: We matched vaccinated naïve (VN) individuals (n = 673) with partial vaccination (n = 64), primary vaccination (n = 590), and primary series plus mRNA vaccine heterologous booster (n = 19) with unvaccinated naturally infected (NI) individuals with a documented primary SARS-CoV-2 infection (n = 206). We measured the levels of neutralizing total antibodies (NTAbs), total antibodies (TAbs), anti-S-RBD IgG, and anti-S1 IgA titers. RESULTS: Homologous primary vaccination with ChAdOx1 not only showed less potent NTAb, TAb, anti-S-RBD IgG, and anti-S1 IgA immune responses compared to primary BNT162b2 or mRNA-1273 vaccination regimens (p < 0.05) but also showed ~3-fold less anti-S1 IgA response compared to infection-induced immunity (p < 0.001). Nevertheless, a heterologous booster led to an increase of ~12 times in the immune response when compared to two consecutive homologous ChAdOx1 immunizations. Furthermore, correlation analyses revealed that both anti-S-RBD IgG and anti-S1 IgA significantly contributed to virus neutralization among NI individuals, particularly in symptomatic and pauci-symptomatic individuals, whereas among VN individuals, anti-S-RBD IgG was the main contributor to virus neutralization. CONCLUSION: The results emphasize the potential benefit of using heterologous mRNA boosters to increase antibody levels and neutralizing capacity particularly in patients who received primary vaccination with ChAdOx1.


2019-nCoV Vaccine mRNA-1273 , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine , COVID-19 Vaccines , COVID-19 , Immunization, Secondary , Immunoglobulin A , Immunoglobulin G , SARS-CoV-2 , Humans , BNT162 Vaccine/immunology , BNT162 Vaccine/administration & dosage , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19/immunology , Male , Immunoglobulin G/blood , Immunoglobulin G/immunology , Female , SARS-CoV-2/immunology , Adult , 2019-nCoV Vaccine mRNA-1273/immunology , Middle Aged , Immunoglobulin A/blood , Immunoglobulin A/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Young Adult , Follow-Up Studies , Vaccination , Aged , Immunogenicity, Vaccine , Antibody Formation/immunology , ChAdOx1 nCoV-19/immunology , ChAdOx1 nCoV-19/administration & dosage , Spike Glycoprotein, Coronavirus/immunology
8.
Curr Microbiol ; 81(7): 171, 2024 May 13.
Article En | MEDLINE | ID: mdl-38739274

A third booster doses for the 2019 coronavirus disease (COVID-19) is widely used all over the world, especially in risky individuals, with the recommendation of WHO. The purpose of this study was to evaluate the effectiveness of mRNA (BNT162b2), and CoronaVac (Sinovac Biotech) vaccines as a reminder dose following two doses of CoronaVac against COVID-19 infection, serious illness, and mortality in the geriatric population aged 75 and older during the delta variant dominant period. Our study comprised 2730 individuals the age of 75 and older in total, of which 1082 (39.6%) were male and 1648 (60.4%) were female. The vaccine effectiveness (VE) of 2 doses of CoronaVac + 1 dose of BNT162b2 vaccine combination against COVID-19 was determined as 89.2% (95% Confidence interval (CI) 80.7-93.9%), while the VE of 3 doses of CoronaVac vaccine was determined as 80.4% (95% CI 60.5-90.2%). Geriatric patients who received three doses of CoronaVac vaccine did not need intensive care. No deaths were observed in the vaccinated groups. While the VE of vaccination with 2 doses of CoronaVac + 1 dose of BNT162b2 was 41.8% (95% CI 0-74.1%) against hospitalization, 64.4% (95% CI 0-94.7%) against intensive care unit admission, the VE of vaccination with three doses of the CoronaVac was 78.2% (95% CI 0-96.5%) against hospitalization. In conclusion, our research showed that, even with the emergence of viral variants, a third dose of the CoronaVac and BNT162b2 vaccines is highly effective against symptomatic SARS-CoV-2 infection. Third-dose vaccination regimens, including heterologous and homologous vaccines, can be an effective tool in controlling the COVID-19 pandemic and the emergence of new variants.


BNT162 Vaccine , COVID-19 Vaccines , COVID-19 , Immunization, Secondary , SARS-CoV-2 , Vaccine Efficacy , Humans , Aged , COVID-19/prevention & control , COVID-19/immunology , Female , Male , Aged, 80 and over , SARS-CoV-2/immunology , SARS-CoV-2/genetics , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , BNT162 Vaccine/administration & dosage , BNT162 Vaccine/immunology , Vaccination
10.
Sci Rep ; 14(1): 8926, 2024 04 18.
Article En | MEDLINE | ID: mdl-38637558

To evaluate immune responses to COVID-19 vaccines in adults aged 50 years and older, spike protein (S)-specific antibody concentration, avidity, and function (via angiotensin-converting enzyme 2 (ACE2) inhibition surrogate neutralization and antibody dependent cellular phagocytosis (ADCP)), as well as S-specific T cells were quantified via activation induced marker (AIM) assay in response to two-dose series. Eighty-four adults were vaccinated with either: mRNA/mRNA (mRNA-1273 and/or BNT162b2); ChAdOx1-S/mRNA; or ChAdOx1-S/ChAdOx1-S. Anti-S IgG concentrations, ADCP scores and ACE2 inhibiting antibody concentrations were highest at one-month post-second dose and declined by four-months post-second dose for all groups. mRNA/mRNA and ChAdOx1-S/mRNA schedules had significantly higher antibody responses than ChAdOx1-S/ChAdOx1-S. CD8+ T-cell responses one-month post-second dose were associated with increased ACE2 surrogate neutralization. Antibody avidity (total relative avidity index) did not change between one-month and four-months post-second dose and did not significantly differ between groups by four-months post-second dose. In determining COVID-19 correlates of protection, a measure that considers both antibody concentration and avidity should be considered.


COVID-19 Vaccines , COVID-19 , Adult , Humans , Middle Aged , Aged , Angiotensin-Converting Enzyme 2 , BNT162 Vaccine , Prospective Studies , COVID-19/prevention & control , Canada/epidemiology , Antibodies , ChAdOx1 nCoV-19 , RNA, Messenger , Antibodies, Viral , Vaccination
11.
Sci Rep ; 14(1): 8982, 2024 04 18.
Article En | MEDLINE | ID: mdl-38637586

Many molecular mechanisms that lead to the host antibody response to COVID-19 vaccines remain largely unknown. In this study, we used serum antibody detection combined with whole blood RNA-based transcriptome analysis to investigate variability in vaccine response in healthy recipients of a booster (third) dose schedule of the mRNA BNT162b2 vaccine against COVID-19. The cohort was divided into two groups: (1) low-stable individuals, with antibody concentration anti-SARS-CoV IgG S1 below 0.4 percentile at 180 days after boosting vaccination; and (2) high-stable individuals, with antibody values greater than 0.6 percentile of the range in the same period (median 9525 [185-80,000] AU/mL). Differential gene expression, expressed single nucleotide variants and insertions/deletions, differential splicing events, and allelic imbalance were explored to broaden our understanding of the immune response sustenance. Our analysis revealed a differential expression of genes with immunological functions in individuals with low antibody titers, compared to those with higher antibody titers, underscoring the fundamental importance of the innate immune response for boosting immunity. Our findings also provide new insights into the determinants of the immune response variability to the SARS-CoV-2 mRNA vaccine booster, highlighting the significance of differential splicing regulatory mechanisms, mainly concerning HLA alleles, in delineating vaccine immunogenicity.


COVID-19 Vaccines , COVID-19 , Humans , SARS-CoV-2/genetics , BNT162 Vaccine , mRNA Vaccines , COVID-19/prevention & control , Antibodies , Immunity, Innate , Antibodies, Viral
12.
JAMA Netw Open ; 7(4): e248051, 2024 Apr 01.
Article En | MEDLINE | ID: mdl-38652471

Importance: There is still considerable controversy in the literature regarding the capacity of intramuscular messenger RNA (mRNA) vaccination to induce a mucosal immune response. Objective: To compare serum and salivary IgG and IgA levels among mRNA-vaccinated individuals with or without previous SARS-CoV-2 infection. Design, Setting, and Participants: In this cohort study, SARS-CoV-2-naive participants and those with previous infection were consecutively included in the CoviCompare P and CoviCompare M mRNA vaccination trials and followed up to day 180 after vaccination with either the BNT162b2 (Pfizer-BioNTech) vaccine or the mRNA-1273 (Moderna) vaccine at the beginning of the COVID-19 vaccination campaign (from February 19 to June 8, 2021) in France. Data were analyzed from October 25, 2022, to July 13, 2023. Main Outcomes and Measures: An ultrasensitive digital enzyme-linked immunosorbent assay was used for the comparison of SARS-CoV-2 spike-specific serum and salivary IgG and IgA levels. Spike-specific secretory IgA level was also quantified at selected times. Results: A total of 427 individuals were included in 3 groups: participants with SARS-CoV-2 prior to vaccination who received 1 single dose of BNT162b2 (Pfizer-BioNTech) (n = 120) and SARS-CoV-2-naive individuals who received 2 doses of mRNA-1273 (Moderna) (n = 172) or 2 doses of BNT162b2 (Pfizer-BioNTech) (n = 135). The median age was 68 (IQR, 39-75) years, and 228 (53.4%) were men. SARS-CoV-2 spike-specific IgG saliva levels increased after 1 or 2 vaccine injections in individuals with previous infection and SARS-CoV-2-naive individuals. After vaccination, SARS-CoV-2-specific saliva IgA levels, normalized with respect to total IgA levels, were significantly higher in participants with previous infection, as compared with the most responsive mRNA-1273 (Moderna) recipients (median normalized levels, 155 × 10-5 vs 37 × 10-5 at day 29; 107 × 10-5 vs 54 × 10-5 at day 57; and 104 × 10-5 vs 70 × 10-5 at day 180 [P < .001]). In contrast, compared with day 1, spike-specific IgA levels in the BNT162b2-vaccinated SARS-CoV-2-naive group increased only at day 57 (36 × 10-5 vs 49 × 10-5 [P = .01]). Bona fide multimeric secretory IgA levels were significantly higher in individuals with previous infection compared with SARS-CoV-2-naive individuals after 2 antigenic stimulations (median optical density, 0.36 [IQR, 0.16-0.63] vs 0.16 [IQR, 0.10-0.22]; P < .001). Conclusions and Relevance: The findings of this cohort study suggest that mRNA vaccination was associated with mucosal immunity in individuals without prior SARS-CoV-2 infection, but at much lower levels than in previously infected individuals. Further studies are needed to determine the association between specific saliva IgA levels and prevention of infection or transmission.


2019-nCoV Vaccine mRNA-1273 , Antibodies, Viral , BNT162 Vaccine , COVID-19 Vaccines , COVID-19 , Immunoglobulin A , Immunoglobulin G , SARS-CoV-2 , Saliva , Humans , Male , Immunoglobulin G/blood , Female , COVID-19/prevention & control , COVID-19/immunology , SARS-CoV-2/immunology , Saliva/immunology , Middle Aged , Adult , Immunoglobulin A/analysis , Immunoglobulin A/blood , Antibodies, Viral/analysis , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Vaccination/methods , Cohort Studies , Aged , Immunity, Mucosal/immunology , France
13.
Cell ; 187(8): 1822-1822.e1, 2024 Apr 11.
Article En | MEDLINE | ID: mdl-38608649

In November 2023, Japan's Ministry of Health, Labour and Welfare granted regulatory approval of ARCT-154, a self-amplifying RNA COVID-19 vaccine developed by Arcturus Therapeutics. Clinical trials showed comparable safety and efficacy using a lower dose compared to the mRNA vaccine BNT162b2. To view this Bench-to-Bedside, open or download the PDF.


COVID-19 Vaccines , mRNA Vaccines , Humans , BNT162 Vaccine , COVID-19/prevention & control , mRNA Vaccines/administration & dosage , mRNA Vaccines/adverse effects
14.
Int J Mol Sci ; 25(7)2024 Mar 22.
Article En | MEDLINE | ID: mdl-38612407

A small fraction of people vaccinated with mRNA-lipid nanoparticle (mRNA-LNP)-based COVID-19 vaccines display acute or subacute inflammatory symptoms whose mechanism has not been clarified to date. To better understand the molecular mechanism of these adverse events (AEs), here, we analyzed in vitro the vaccine-induced induction and interrelations of the following two major inflammatory processes: complement (C) activation and release of proinflammatory cytokines. Incubation of Pfizer-BioNTech's Comirnaty and Moderna's Spikevax with 75% human serum led to significant increases in C5a, sC5b-9, and Bb but not C4d, indicating C activation mainly via the alternative pathway. Control PEGylated liposomes (Doxebo) also induced C activation, but, on a weight basis, it was ~5 times less effective than that of Comirnaty. Viral or synthetic naked mRNAs had no C-activating effects. In peripheral blood mononuclear cell (PBMC) cultures supplemented with 20% autologous serum, besides C activation, Comirnaty induced the secretion of proinflammatory cytokines in the following order: IL-1α < IFN-γ < IL-1ß < TNF-α < IL-6 < IL-8. Heat-inactivation of C in serum prevented a rise in IL-1α, IL-1ß, and TNF-α, suggesting C-dependence of these cytokines' induction, although the C5 blocker Soliris and C1 inhibitor Berinert, which effectively inhibited C activation in both systems, did not suppress the release of any cytokines. These findings suggest that the inflammatory AEs of mRNA-LNP vaccines are due, at least in part, to stimulation of both arms of the innate immune system, whereupon C activation may be causally involved in the induction of some, but not all, inflammatory cytokines. Thus, the pharmacological attenuation of inflammatory AEs may not be achieved via monotherapy with the tested C inhibitors; efficacy may require combination therapy with different C inhibitors and/or other anti-inflammatory agents.


COVID-19 , Complement Inactivating Agents , Nanoparticles , Humans , Liposomes , COVID-19 Vaccines/adverse effects , Leukocytes, Mononuclear , Cytokines , Tumor Necrosis Factor-alpha , BNT162 Vaccine , Complement Activation , Lipids
15.
Swiss Med Wkly ; 154: 3708, 2024 Mar 27.
Article En | MEDLINE | ID: mdl-38639178

BACKGROUND: Knowing whether shift work negatively affects the immune system's response to COVID-19 vaccinations could be valuable for planning future vaccination campaigns for healthcare workers. We aimed to determine the impact of working late or night shifts on serum anti-SARS-CoV-2 spike protein immunoglobulin G (anti-S) antibody levels after primary SARS-CoV-2-mRNA vaccination. METHODS: To obtain detailed information on shift work, we sent a separate online questionnaire to 1475 eligible healthcare workers who participated in a prospective longitudinal study conducted in 15 healthcare institutions in Switzerland. We asked all vaccinated healthcare workers with available anti-S antibody levels after vaccination to complete a brief online survey on their working schedules within one week before and after primary mRNA vaccination. We used multivariate regression to evaluate the association between work shifts around primary vaccination and anti-S antibody levels. We adjusted for confounders already known to influence vaccine efficacy (e.g. age, sex, immunosuppression, and obesity) and for variables significant at the 0.05 alpha level in the univariate analyses. RESULTS: The survey response rate was 43% (n = 638). Ninety-eight responders were excluded due to unknown vaccination dates, different vaccines, or administration of the second dose shortly (within 14 days) after or before serologic follow-up. Of the 540 healthcare workers included in our analysis, 175 (32.4%) had worked at least one late or night shift within seven days before and/or after primary vaccination. In the univariate analyses, working late or night shifts was associated with a nonsignificant -15.1% decrease in serum anti-S antibody levels (p = 0.090). In the multivariate analysis, prior infection (197.2% increase; p <0.001) and immunisation with the mRNA-1273 vaccine (63.7% increase compared to the BNT162b2 vaccine; p <0.001) were the strongest independent factors associated with increased anti-S antibody levels. However, the impact of shift work remained statistically nonsignificant (-13.5%, p = 0.108). CONCLUSION: Working late or night shifts shortly before or after mRNA vaccination against COVID-19 does not appear to significantly impact serum anti-S antibody levels. This result merits consideration since it supports flexible vaccination appointments for healthcare workers, including those working late or night shifts.


Antibodies, Viral , COVID-19 , Shift Work Schedule , Vaccination , Humans , 2019-nCoV Vaccine mRNA-1273 , Antibodies, Viral/blood , BNT162 Vaccine , COVID-19/blood , COVID-19/prevention & control , Health Personnel , Longitudinal Studies , Prospective Studies , Retrospective Studies , SARS-CoV-2 , Spike Glycoprotein, Coronavirus , Switzerland
16.
Front Cell Infect Microbiol ; 14: 1371695, 2024.
Article En | MEDLINE | ID: mdl-38638823

Introduction: SARS-CoV-2 vaccines production and distribution enabled the return to normalcy worldwide, but it was not fast enough to avoid the emergence of variants capable of evading immune response induced by prior infections and vaccination. This study evaluated, against Omicron sublineages BA.1, BA.5 and BQ.1.1, the antibody response of a cohort vaccinated with a two doses CoronaVac protocol and followed by two heterologous booster doses. Methods: To assess vaccination effectiveness, serum samples were collected from 160 individuals, in 3 different time points (9, 12 and 18 months after CoronaVac protocol). For each time point, individuals were divided into 3 subgroups, based on the number of additional doses received (No booster, 1 booster and 2 boosters), and a viral microneutralization assay was performed to evaluate neutralization titers and seroconvertion rate. Results: The findings presented here show that, despite the first booster, at 9m time point, improved neutralization level against omicron ancestor BA.1 (133.1 to 663.3), this trend was significantly lower for BQ.1.1 and BA.5 (132.4 to 199.1, 63.2 to 100.2, respectively). However, at 18m time point, the administration of a second booster dose considerably improved the antibody neutralization, and this was observed not only against BA.1 (2361.5), but also against subvariants BQ.1.1 (726.1) and BA.5 (659.1). Additionally, our data showed that, after first booster, seroconvertion rate for BA.5 decayed over time (93.3% at 12m to 68.4% at 18m), but after the second booster, seroconvertion was completely recovered (95% at 18m). Discussion: Our study reinforces the concerns about immunity evasion of the SARS-CoV-2 omicron subvariants, where BA.5 and BQ.1.1 were less neutralized by vaccine induced antibodies than BA.1. On the other hand, the administration of a second booster significantly enhanced antibody neutralization capacity against these subvariants. It is likely that, as new SARS-CoV-2 subvariants continue to emerge, additional immunizations will be needed over time.


BNT162 Vaccine , COVID-19 Vaccines , Vaccines, Inactivated , Humans , Antibodies, Viral , Immunization , SARS-CoV-2 , Antibodies, Neutralizing
17.
Nat Commun ; 15(1): 3368, 2024 Apr 20.
Article En | MEDLINE | ID: mdl-38643233

The immune escape of Omicron variants significantly subsides by the third dose of an mRNA vaccine. However, it is unclear how Omicron variant-neutralizing antibodies develop under repeated vaccination. We analyze blood samples from 41 BNT162b2 vaccinees following the course of three injections and analyze their B-cell receptor (BCR) repertoires at six time points in total. The concomitant reactivity to both ancestral and Omicron receptor-binding domain (RBD) is achieved by a limited number of BCR clonotypes depending on the accumulation of somatic hypermutation (SHM) after the third dose. Our findings suggest that SHM accumulation in the BCR space to broaden its specificity for unseen antigens is a counterprotective mechanism against virus variant immune escape.


COVID-19 Vaccines , COVID-19 , Humans , BNT162 Vaccine , COVID-19/prevention & control , SARS-CoV-2/genetics , Antibodies, Neutralizing , Antibodies, Viral
18.
Spinal Cord Ser Cases ; 10(1): 30, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38664389

INTRODUCTION: Acute transverse myelitis (ATM) is a rare neurological complication of Coronavirus disease (COVID-19) vaccines. Various vaccines have been linked to ATM, such as non-replicating viral vectors, ribonucleic acid, and inactivated vaccines. An ATM case is presented here involving the BNT162b2 vaccine leading to asymmetrical incomplete paraplegia and neurogenic bladder. CASE PRESENTATION: A 66-year-old male developed urinary retention one day after his second dose of the BNT162b2 vaccine, followed by rapidly progressing lower limb weakness. Clinical examination showed asymmetrical paraparesis, reduced sensation below the T8 level, including perianal sensation, and loss of ankle and anal reflexes. Laboratory tests were largely unremarkable, while the spine MRI revealed thickened conus medullaris with a mild increase in T2/STIR signal intensity and subtle enhancement post gadolinium. Following treatment with methylprednisolone, plasmapheresis, and immunoglobulin, and a rehabilitation program, the patient achieved good motor and sensory recovery, but the bladder dysfunction persisted. Single-channel cystometry indicated neurogenic detrusor underactivity and reduced bladder sensation, as evidenced by low-pressure and compliant bladder. The urethral sphincter appeared intact or overactive. The post-void residual urine was significant, necessitating prolonged intermittent catheterisation. DISCUSSION: Bladder dysfunction due to the COVID-19 vaccine-associated ATM is not as commonly reported as motor or sensory deficits. To our knowledge, this is the first case to highlight a neurogenic bladder that necessitates prolonged intermittent catheterisation as a consequence of COVID-19 vaccine-associated ATM. This report highlights the rare complication of the neurogenic bladder resulting from the BNT162b2 vaccine. Early detection and treatment are crucial to prevent long-term complications.


BNT162 Vaccine , COVID-19 Vaccines , Myelitis, Transverse , Urinary Bladder, Neurogenic , Humans , Male , Myelitis, Transverse/etiology , Aged , Urinary Bladder, Neurogenic/etiology , Urinary Bladder, Neurogenic/therapy , BNT162 Vaccine/adverse effects , COVID-19 Vaccines/adverse effects , COVID-19/complications
19.
Vaccine ; 42(12): 2951-2954, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38584057

Heterologous Sinovac-CoronaVac booster(s) in 12-17-year-olds who had a moderate/severe reaction to Pfizer-BNT162b2 mRNA vaccine was found to safe with no serious adverse events reported. In those primed with 1 dose of Pfizer-BNT162b2 vaccine, subsequent boosters with 2 doses of Sinovac-CoronaVac vaccines achieved neutralizing antibody levels which were comparable to those who had received 2 doses of Pfizer-BNT162b2 vaccines followed by 1 dose of Sinovac-CoronaVac vaccination. Adolescents with 1 Pfizer-BNT162b2 followed by 2 Sinovac-CoronaVac vaccines developed T-cell responses against broad peptides including membrane, nucleoprotein 1 and 2 but levels were highest for Spike protein and lasted until day 150 post-vaccination.


BNT162 Vaccine , Vaccination , Vaccines, Inactivated , Adolescent , Humans , Antibodies, Neutralizing , Antibodies, Viral , BNT162 Vaccine/adverse effects , Vaccination/adverse effects , Vaccines, Inactivated/adverse effects , Child
20.
Disaster Med Public Health Prep ; 18: e66, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38618867

OBJECTIVE: 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. METHODS: A longitudinal study was conducted from June 1, 2021, to June 30, 2022, and 300 participants were included through simple random sampling. RESULTS: 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. CONCLUSIONS: 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.


COVID-19 Vaccines , COVID-19 , Humans , COVID-19 Vaccines/adverse effects , BNT162 Vaccine , SARS-CoV-2 , Longitudinal Studies , COVID-19/epidemiology , COVID-19/prevention & control , Immunoglobulin G
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