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Waning antibodies in SARS-CoV-2 naïve vaccinees: Results of a three-month interim analysis of ongoing immunogenicity and efficacy surveillance of the mRNA-1273 vaccine in healthcare workers

2021; Elsevier BV; Volume: 83; Issue: 3 Linguagem: Inglês

10.1016/j.jinf.2021.06.017

1532-2742

Marie Tré‐Hardy, Roberto Cupaiolo, Alain Wilmet, Ingrid Beukinga, Laurent Blairon,

Bacillus and Francisella bacterial research

•A close follow-up of vaccinees remains crucial to confirm both safety and long-lasting immune protection.•Three months after vaccination, we confirm a very high efficacy and a persistence of anti-spike antibodies.•The antibody decrease observed in some seronegative participants argues for an additional dose of vaccine for this specific subgroup. We read with interest the study recently published by Capetti and colleagues showing one-year durability of anti-spike IgG after natural exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).1Capetti AF Borgonovo F Mileto D Gagliardi G Mariani C Lupo A et al.One-year durability of anti-spike IgG to SARS-CoV-2: Preliminary data from the anticrown prospective observational study one year durability of COVID-19 anti-spike IgG.J Infect. 2021; https://doi.org/10.1016/j.jinf.2021.05.023Abstract Full Text Full Text PDF Scopus (12) Google Scholar Although the antibody kinetics in symptomatic and asymptomatic patients is known,1Capetti AF Borgonovo F Mileto D Gagliardi G Mariani C Lupo A et al.One-year durability of anti-spike IgG to SARS-CoV-2: Preliminary data from the anticrown prospective observational study one year durability of COVID-19 anti-spike IgG.J Infect. 2021; https://doi.org/10.1016/j.jinf.2021.05.023Abstract Full Text Full Text PDF Scopus (12) Google Scholar,2Meyer B. Waning antibodies to SARS-CoV-2 - Don't panic.Lancet Reg Health Eur. 2021; 4100115https://doi.org/10.1016/j.lanepe.2021.100115Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar we still ignore how it evolve beyond 6 months in vaccinees and if and how the initial serological status of vaccinees might influence it. To date, antibody kinetics data after vaccination remain fragmented. The study by Doria-Rose et al., showed persistence of antibodies 6 months after the second dose of mRNA-1273 vaccine in 33 participants included in the phase 1 follow-up of the Moderna study without knowing their initial serological status before the vaccination.3Doria-Rose N Suthar MS Makowski M O'Connell S McDermott AB Flach B et al.Antibody Persistence through 6 Months after the Second Dose of mRNA-1273 Vaccine for Covid-19.N Engl J Med. 2021; https://doi.org/10.1056/NEJMc2103916Crossref Scopus (488) Google Scholar Likewise, interim results from a phase 3 trial of the mRNA-1273 vaccine indicated 94.5% efficacy in preventing coronavirus disease 2019 (Covid-19).4Baden LR El Sahly HM Essink B Kotloff K Frey S Novak R et al.Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.N Engl J Med. 2021; 384: 403-416https://doi.org/10.1056/NEJMoa2035389Crossref PubMed Scopus (6646) Google Scholar Since efficacy trials have focused on individuals without prior exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), little is known about the immune responses induced by mRNA-1273 in participants who have suffered from Covid-19. Finally, this large-scale, phase 3 study conducted by the firm Moderna was carried out from July 27 to October 23, 2020, away from the worrying spread of new SARS-CoV-2 variants.5Wu K Werner AP Koch M Choi A Narayanan E Stewart-Jones GBE et al.Serum Neutralizing Activity Elicited by mRNA-1273 Vaccine.N Engl J Med. 2021; 384: 1468-1470https://doi.org/10.1056/NEJMc2102179Crossref PubMed Scopus (288) Google Scholar, 6Hacisuleyman E Hale C Saito Y Blachere NE Bergh M Conlon EG et al.Vaccine Breakthrough Infections with SARS-CoV-2 Variants.N Engl J Med. 2021; https://doi.org/10.1056/NEJMoa2105000Crossref Scopus (485) Google Scholar, 7Ramanathan M Ferguson ID Miao W Khavari PA SARS-CoV-2 B.1.1.7 and B.1.351 spike variants bind human ACE2 with increased affinity.Lancet Infect Dis. 2021; https://doi.org/10.1016/S1473-3099(21)00262-0Abstract Full Text Full Text PDF PubMed Scopus (139) Google Scholar In our independent study, we compared the antibody response 2 weeks after the first injection (T1) (median time [± 95% CI]: 16 [± 2.26] days), 2 weeks after the second injection (T2) (median time [± 95% CI]: 14 [± 1.83] days) and 3 months after the first injection (T3) (median time [± 95% CI]: 86 [± 4.59] days) from 205 healthcare workers (HCWs) stratified according to their initial serological status. The quantitative analysis of the anti-SARS-CoV-2 IgG antibodies directed against the subunits (S1) and (S2) of the virus spike protein was carried out using the LIAISON®SARS-CoV-2 IgG kit (DiaSorin®, Saluggia, Italy) previously validated in our laboratory8Tré-Hardy M Wilmet A Beukinga I Dogné JM Douxfils J Blairon L. Validation of a chemiluminescent assay for specific SARS-CoV-2 antibody.Clin Chem Lab Med. 2020; 58: 1357-1364https://doi.org/10.1515/cclm-2020-0594Crossref PubMed Scopus (68) Google Scholar and also used by Capetti et al.1Capetti AF Borgonovo F Mileto D Gagliardi G Mariani C Lupo A et al.One-year durability of anti-spike IgG to SARS-CoV-2: Preliminary data from the anticrown prospective observational study one year durability of COVID-19 anti-spike IgG.J Infect. 2021; https://doi.org/10.1016/j.jinf.2021.05.023Abstract Full Text Full Text PDF Scopus (12) Google Scholar Effectiveness of the mRNA-1273 vaccine was also assessed through a medical questionnaire. Participants were asked to declare any results of RT-qPCR tests regardless of the reason behind, even in asymptomatic situations, and any eventual Covid-19 infection after vaccination (including severity of symptoms). To better apprehend the observed efficacy, a comparison of the level of antibodies directed against the nucleocapsid was carried out on part of the cohort of seronegative participants at T0 and T3 with the Platelia® SARS-CoV-2 Total Ab test (Bio-Rad®, Marnes-la-Coquette, France) detecting total antibodies (IgM, IgA and IgG) (n = 86/161). Since only these antibodies are produced during a natural infection, their detection allows us to identify the participants who have been infected by SARS-CoV-2 since their vaccination. In the initially seronegative participants (n = 161), we observed a persistence of anti-S-antibody levels 3 months after vaccination with nevertheless a decrease in the antibody levels observed between T2 and T3 in 48 participants (Fig. 1A). Conversely, an increase in antibody levels was observed in 15 seronegative HCWs. Interestingly, in seropositive people (n = 44), no drop in antibody was observed between T2 and T3. The measured levels are all above the maximum quantification value (> 400 AU/mL). Moreover, the administration of a second dose of vaccine in participants initially seropositive made it possible to catch-up the very few vaccinees (n = 5) with a weaker response at T1 by reaching the maximum level of antibodies at T2 (Fig. 1B). Analysis of the clinical follow-up questionnaires revealed that none of the respondents reported thinking they had been infected (n = 167). Thirty-six of them had to undergo a RT-qPCR and all were negative. Finally, among the seronegative ones, only 2 participants developed antibodies directed against the nucleocapsid at T3 while all were negative at T0 (n = 86). Based on these results and given that none of the participants developed symptoms, the mRNA-1273 vaccine is effective at preventing Covid-19 illness. However, additional long-term serosurveillance studies based on larger cohorts will be necessary to confirm these observations. Monitoring of anti-nucleocapsid antibodies remains a complementary aid in detecting infections which are sometimes asymptomatic in vaccinated persons known to be initially seronegative. Faced with an unprecedented global vaccine deployment, a close follow-up of vaccinees remains crucial to confirm both safety and long-lasting immune protection. In this study, we evaluated the immune response of the participants but also the effectiveness of the mRNA-1273 vaccine in a context different from the previous phase 1 and 3 studies by Moderna, under a higher virological pressure, and by categorizing the participants into 2 cohorts according to their serological status at initiation. Three months after vaccination, we confirm a very high efficacy and a persistence of anti-spike antibodies. However, the decrease observed in some seronegative participants argues for an additional dose of vaccine in the upcoming months for this specific subgroup. This study has been approved by the Ethical Committee of the HIS-IZZ (ethical agreement number: CEHIS/2021–7). None declared.