The BNT162b2 vaccine has been shown to be 95% effective against coronavirus disease 2019 (Covid-19).1 To date, a two-dose vaccine protocol has not been approved in Israel for individuals previously infected with severe acute coronavirus 2 syndrome (SARS-CoV-2); however, the administration of a single dose is now being considered.
In addition to the original virus first identified in Wuhan, China, SARS-CoV-2 variants first identified in the United Kingdom (B.1.1.7), South Africa (B.1.351) and Brazil (P.1) were detected in recent months. .2 Samples of persons vaccinated or previously infected with the original virus or variant B.1.1.7 were shown to have significantly less neutralizing activities against variant B.1.351 than against other variants.3.4 In this study, we investigated whether a single dose of BNT162b2 vaccine would increase neutralizing activity according to variants B.1.1.7, B.1.351, and P.1 in individuals previously infected with SARS-CoV-2.
Serum samples from six patients previously infected with severe acute coronavirus 2 respiratory syndrome (SARS-CoV-2), obtained 1 to 12 weeks after natural infection, immediately before receiving a single dose of BNT162b2 vaccine and 1 to 2 weeks after vaccination tested with a microneutralization test for neutralization response to sub-line B.1 of the original virus (Panel A), variant B.1.1.7 first identified in the United Kingdom (Panel B), variant B.1.351 first identified in South Africa (Panel C) and variant P.1 which was first identified in Brazil (Panel D). Dashed lines indicate the cut-off titer. Solid lines and numbers indicate the geometric mean titer, and dashes show a 95% confidence interval.
Microneutralization analysis with source virus isolates (subline B.1) and variants B.1.1.7, B.1.351 and P.1 was performed on 18 serum samples from six healthcare workers previously infected with SARS-CoV-2, with a sample obtained from each patient in three time periods: 1 to 12 weeks after natural infection, immediately before vaccination, and 1 to 2 weeks after vaccination (Table S1 in the Appendix, available with the full text of this letter at NEJM.org). All six health workers were women (aged 32 to 67 years) and were infected with the original virus (subline B.1), as determined by SARS-CoV-2 sequencing performed at the time of diagnosis. Samples obtained at the first time point had neutralizing activity against the original virus and variants B.1.1.7 and P.1, with geometric mean titers of 456, 256 and 71, respectively, but had little or no neutralizing activity against Variant B.1.351 , with a geometric mean titer of 8. At the second time point, the geometric mean titers were 81, 40, 36, and 7 for the original virus and B.1.1.7, P.1, and B. 1,351 variants. It should be noted that at the third time point, the geometric mean titers were 9195, 8192, 2896 and 1625 for the original virus and variants B.1.1.7, P.1 and B.1.351, i.e. Post-vaccination titers were 114, 203, 81 and 228 times higher than the titers immediately before vaccination (Figure 1 and Table C2).
This study showed that in our small cohort, a single dose of vaccine significantly increased neutralizing activity according to all tested variants, with similar titers detected in patients for each variant. This underscores the importance of vaccination even in previously infected patients, given the added benefit of an increased antibody response to the tested variants. Limitations of the study include a small cohort of women only and a lack of evaluation of T-cell responses. However, we think that the fact that all six patients reacted similarly to vaccination supports our conclusions. Further studies could investigate the effects of the second dose of vaccine on neutralizing activity against worrying variations in persons who have and persons who have not been previously infected.
Yaniv Lustig, Ph.D.
Dr. Ital Nemet
Limor Kliker, M.Sc.
Dr. Neta Zuckerman
Ministry of Health, Tel Hashomer, Israel
Dr. Ruti Yishai
Sharon Alroy-Preis, Ph.D. Med
Ministry of Health, Jerusalem, Israel
Dr. Ella Mendelson
Michal Mandelboim, Ph.D.
Ministry of Health, Tel Hashomer, Israel
Forms for publishing data submitted by the authors are available with the full text of this letter at NEJM.org.
This letter was published on April 7, 2021 on NEJM.org.
Dr. Lustig, Nemet, and Mrs. Clicker contributed equally to this letter.
1. Baden LR,, El Sahly HM,, Essink B, et al. Efficacy and safety of mRNA-1273 SARS-CoV-2. N Engl J Med 2021; 384403–416.
2 Fontanet A,, Autran B,, Lina B,, MP Kieny,, Karim SSA,, Sridhar D. SARS-CoV-2 variants and the end of the COVID-19 pandemic. Lancet 2021; 397:952–954.
3 Liu Y,, Liu J.,, Xia H, et al. Neutralizing serum activity induced by BNT162b2 – preliminary report. N Engl J Med. 10.1056 / NEJMc2102017.
4. Wang P,, Nair MS,, Liu L, et al. Antibody resistance to SARS-CoV-2 variants B.1.351 and B.1.1.7. February 12,, 2021 (https://www.biorxiv.org/content/10.1101/2021.01.25.428137v3). overprint.