Long-lasting neutralizing antibody responses in SARS-CoV-2 seropositive individuals are robustly boosted by immunization with the CoronaVac and BNT162b2 vaccines

Abstract

The durability of circulating neutralizing antibody (nAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their boosting by vaccination remains to be defined. We show that outpatient and hospitalized SARS-CoV-2 seropositive individuals mount a robust neutralizing antibody (nAb) response that peaks at days 23 and 27 post-symptom onset, respectively. Although nAb titers remained higher in hospitalized patients, both study groups showed long-lasting nAb responses that can persist for up to 12 months after natural infection. These nAb responses in previously seropositive individuals can be significantly boosted through immunization with two doses of the CoronaVac (Sinovac) or one dose of the BNT162b2 (BioNTech/Pfizer) vaccines, suggesting a substantial induction of B cell memory responses. Noteworthy, three obese previously seropositive individuals failed to mount a booster response upon vaccination, warranting further studies in this population. Immunization of naïve individuals with two doses of the CoronaVac vaccine or one dose of the BNT162b2 vaccine elicited similar levels of nAbs compared to seropositive individuals 4.2 to 13.3 months post-infection with SARS-CoV-2. Thus, this preliminary evidence suggests that both, seropositive and naïve individuals, require two doses of CoronaVac to ensure the induction of robust nAb titers.

Figure 1.. Neutralizing antibody responses to SARS-CoV-2 in seropositive and naïve individuals before and after CoronaVac or BNT162b2 vaccination.

(Panels A to D) The half-maximum inhibitory concentration (IC50) of sera was determined by microneutralization assay of recombinant vesicular stomatitis virus carrying SARS-CoV-2 spike protein (rVSV-SARS2-S). (Panel A) Neutralizing antibody (nAb) titers (IC50) from 15 outpatients (57 samples; grey circles) and 26 hospitalized (84 samples; red circles) at 2 to 36 days post-symptom onset. Second order polynomial (quadratic) curve fitting was used to establish the days at which peak titers occurred (Ymax). (Panel B) Longitudinal nAb titers from 36 outpatients (66 samples) and 31 hospitalized (44 samples) taken from day 27 (outpatients) or day 23 (hospitalized) until day 414 post-symptom onset. One-phase decay fit is indicated as a bold line, while continuous decay fit is shown with the thinner line in red and gray for the corresponding patient group. (Panel C) nAb titers from 13 outpatient (26 samples) or 14 hospitalized (28 samples) individuals immunized with one or two doses of CoronaVac (24 participants) or one or two doses of BNT162b2 (3 participants) vaccines. (Panel D) nAb titers from naïve individuals after the first and second dose of CoronaVac (11 participants) or BNT162b2 (10 participants) vaccines, compared to seropositive individuals who were not vaccinated (26 participants) or received one dose (8 samples) or two doses (20 samples) of the indicated vaccines. Geometric means with 95% confidence intervals are shown. Circles, non-vaccinated; squares, vaccinated with CoronaVac; triangles, vaccinated with BNT162b2. Dashed line indicates the limit of detection (LOD) of the microneutralization assay. Statistics were performed using unpaired two-tailed Mann-Whitney test. ***P<0.001; ****P<0.0001; ns, non-significant.