Determinants of early antibody responses to COVID-19 mRNA vaccines in a cohort of exposed and naïve healthcare workers

Abstract

Background Two doses of mRNA vaccination have shown >94% efficacy at preventing COVID-19 mostly in naïve adults, but it is not clear if the second dose is needed to maximize effectiveness in those previously exposed to SARS-CoV-2 and what other factors affect responsiveness. Methods We measured IgA, IgG and IgM levels against SARS-CoV-2 spike (S) and nucleocapsid (N) antigens from the wild-type and S from the Alpha, Beta and Gamma variants of concern, after BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccination in a cohort of health care workers (N=578). Neutralizing capacity and antibody avidity were evaluated. Data were analyzed in relation to COVID-19 history, comorbidities, vaccine doses, brand and adverse events. Findings Vaccination induced robust IgA and IgG levels against all S antigens. Neutralization capacity and S IgA and IgG levels were higher in mRNA-1273 vaccinees, previously SARS-CoV-2 exposed, particularly if symptomatic, and in those experiencing systemic adverse effects (p<0·05). A second dose in pre-exposed did not increase antibody levels. Smoking and comorbidities were associated with 43% (95% CI, 19-59) and 45% (95% CI, 63-18) lower neutralization, respectively, and 35% (95% CI, 3-57%) and 55% (95% CI, 33-70%) lower antibody levels, respectively. Among fully vaccinated, 6·3% breakthroughs were detected up to 189 days post-vaccination. Among pre-exposed non-vaccinated, 90% were IgG seropositive more than 300 days post-infection. Interpretation Our data support administering a single-dose in pre-exposed healthy individuals as primary vaccination. However, heterogeneity of responses suggests that personalized recommendations may be necessary depending on COVID-19 history and life-style. Higher mRNA-1273 immunogenicity would be beneficial for those expected to respond worse to vaccination and in face of variants that escape immunity such as Omicron. Persistence of antibody levels in pre-exposed unvaccinated indicates maintenance of immunity up to one year. Funding This work was supported by Institut de Salut Global de Barcelona (ISGlobal) internal funds, in-kind contributions from Hospital Clínic de Barcelona, the Fundació Privada Daniel Bravo Andreu, and European Institute of Innovation and Technology (EIT) Health (grant number 20877), supported by the European Institute of Innovation and Technology, a body of the European Union receiving support from the H2020 Research and Innovation Programme. We acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. L. I. work was supported by PID2019-110810RB-I00 grant from the Spanish Ministry of Science & Innovation. Development of SARS-CoV-2 reagents was partially supported by the National Institute of Allergy and Infe...

The Effect of Smoking on Humoral Response to COVID-19 Vaccines: A Systematic Review of Epidemiological Studies

“…Another report did not specify the enrolled population. In 17 out of 23 studies, current smokers showed significant lower antibody titre, and in a few reports, highlighted a more rapid lowering of the vaccine-elicited IgG compared with nonsmokers [19,20,[26][27][28][29][30]32,34,[36][37][38][39][40][41]43,44]. In particular, accelerated antibody decline was reported in the prospective assessments by Ferrara et al [20], Zhang et al [27], and Malavazos et al [30].…”

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“…A robust IgA and IgG response has been evoked in individuals receiving either BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccination (n = 578). The neutralization was higher in mRNA-1273 vaccinees those previously had symptomatic SARS-CoV-2 infection ( Moncunill et al, 2022 ). Though the Omicron variant compromised the effectiveness of 2 doses of mRNA vaccination and reduced overall protection, it can still protect against severe consequences ( Tanne, 2021a ).…”

Decreased and Heterogeneous Neutralizing Antibody Responses Against RBD of SARS-CoV-2 Variants After mRNA Vaccination

“…Finally, we cannot exclude that differences in the timing of sample collection after vaccination may affect, in some cases, the variations observed in the levels of RBD-specific neutralizing antibodies between individuals within the same group. Yet, there are other factors intrinsic to the individuals that may also contribute to the heterogeneity of responses, including age, comorbidities, or smoking habits, as we have previously reported ( 21 ).…”

“…Plasma sample dilutions used reflect the different levels of neutralizing antibodies produced after vaccination as compared to those in naturally exposed individuals. These dilutions were selected based on a previous report of a cohort of healthcare workers that included the study population analyzed here, in which we evaluated the levels of neutralizing antibodies against WT RBD in SARS-CoV-2 exposed non-vaccinated subjects (after one year follow-up) and in individuals receiving the Moderna or Pfizer-BioNTech vaccines ( 21 ). Cells were stained with anti-mouse IgG-PE (Jackson ImmunoResearch), washed, and analyzed by flow cytometry using standard procedures.…”