Evaluation of the Immune Response Induced by CoronaVac 28-Day Schedule Vaccination in a Healthy Population Group

Alejandro Escobar, Felipe E Reyes-López, Mónica L Acevedo, Luis Alonso-Palomares, Fernando Valiente-Echeverría, Ricardo Soto-Rifo, Hugo Portillo, Jimena Gatica, Ivan Flores, Estefanía Nova-Lamperti, Carlos Barrera-Avalos, María Rosa Bono, Leonardo Vargas, Valeska Simon, Elias Leiva-Salcedo, Cecilia Vial, Juan Hormazabal, Lina Jimena Cortes, Daniel Valdés, Ana M Sandino, Mónica Imarai, Claudio Acuña-Castillo, Alejandro Escobar, Felipe E Reyes-López, Mónica L Acevedo, Luis Alonso-Palomares, Fernando Valiente-Echeverría, Ricardo Soto-Rifo, Hugo Portillo, Jimena Gatica, Ivan Flores, Estefanía Nova-Lamperti, Carlos Barrera-Avalos, María Rosa Bono, Leonardo Vargas, Valeska Simon, Elias Leiva-Salcedo, Cecilia Vial, Juan Hormazabal, Lina Jimena Cortes, Daniel Valdés, Ana M Sandino, Mónica Imarai, Claudio Acuña-Castillo

Abstract

CoronaVac vaccine from Sinovac Life Science is currently being used in several countries. In Chile, the effectiveness of preventing hospitalization is higher than 80% with a vaccination schedule. However, to date, there are no data about immune response induction or specific memory. For this reason, we recruited 15 volunteers without previous suspected/diagnosed COVID-19 and with negative PCR over time to evaluate the immune response to CoronaVac 28 and 90 days after the second immunization (dpi). The CoronaVac administration induces total and neutralizing anti-spike antibodies in all vaccinated volunteers at 28 and 90 dpi. Furthermore, using ELISpot analysis to assay cellular immune responses against SARS-CoV-2 spike protein, we found an increase in IFN-gamma- and Granzyme B-producing cells in vaccinated volunteers at 28 and 90 dpi. Together, our results indicate that CoronaVac induces a robust humoral immune response and cellular immune memory of at least 90 dpi.

Keywords: COVID-19; CoronaVac; SARS-CoV-2; herd immunity; immunological memory; neutralizing antibodies; vaccine.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Escobar, Reyes-López, Acevedo, Alonso-Palomares, Valiente-Echeverría, Soto-Rifo, Portillo, Gatica, Flores, Nova-Lamperti, Barrera-Avalos, Bono, Vargas, Simon, Leiva-Salcedo, Vial, Hormazabal, Cortes, Valdés, Sandino, Imarai and Acuña-Castillo.

Figures

Figure 1
Figure 1
Pro- and anti-inflammatory cytokines in the plasma from CoronaVac-vaccinated volunteers. The levels of (A) IL-8, (B) IL-12, (C) IL-6, (D) IL-1β, (E) IL-10, and (F) TNF-α were measured by flow cytometry as described in Materials and Methods. Data represented the cytokine level on each volunteer before (Day 0) and 28 days after the second immunization (dpi). The data show individual paired values. Asterisk (**) represents significant difference (p < 0.01). n/s indicates non-significant differences.
Figure 2
Figure 2
Total anti-S antibodies in the plasma of CoronaVac-vaccinated volunteers. Anti-S antibodies were quantified in plasma obtained prior to immunization (Day 0), and 28 and 90 days after the second immunization (dpi). (A) Antibody titers are expressed as the area under the ELISA OD curve (AUC) made from four serial dilutions (1/200, 1/400, 1/800, and 1/1600) for each volunteer (▾). The data show individual paired values. (B) Detail of the antibody titers for the volunteers with complete follow-up (n = 15) throughout the study (data from A;○), and those with no sample on some of the time points evaluated (•) were graphed and shown with median. Asterisk (*) represents statistically significant difference compared to baseline (p < 0.05). Hashtag (#) represents statistically significant difference between 28 dpi and 90 dpi samples. n/s, not significant (p < 0.05).
Figure 3
Figure 3
Total anti-S neutralizing antibodies in the plasma of CoronaVac-vaccinated volunteers. The neutralization curves from plasma samples of volunteers were obtained by using a pseudotyped viral particle (HIV-1–SΔ19). Samples were titrated in triplicate at serial threefold dilutions and expressed as percent of neutralization. (A) Total anti-S neutralizing antibodies before vaccination (Day 0). (B) Total anti-S neutralizing antibodies at 28 days after the second immunization (dpi). (C) Total anti-S neutralizing antibodies at 90 dpi (D) IC50 calculated based on inhibition rates and depicted for each sample obtained from volunteers with a complete follow-up schedule (□) (n = 15). The data show individual paired values. (E) IC50 calculated for the total data (n = 21 volunteers, including those with no complete follow-up schedule) were graphed and shown with median. Open circles (○): data from (D) Black circles (•): volunteers with no sample on some of the time-points evaluated. Asterisk (*) represents statistically significant difference obtained from the comparison against day 0 (p < 0.05). Hashtag (#) represents statistically significant difference between 28 dpi and 90 dpi samples. n/s, not significant (p < 0.05).
Figure 4
Figure 4
Cytokine secreting cells of vaccinated volunteers in vitro induced by SARS-CoV-2 S protein. (A) IFN-γ (○). (B) Granzyme (•). The number of ELISPOT-forming cells (SFC) per 3 × 105 was quantitated in PBMC, obtained before vaccination (indicated as "Day 0"). Twenty-eight and 90 days after the second immunization (dpi) (n = 15 volunteers), the data show individual paired values. (C) Total data from 21 volunteers (same volunteers from (A, B) and others with no sample on some of the time points evaluated) were graphed and shown with median for IFN-γ (○) and Granzyme (•). Asterisk (*) represents statistically significant difference (p < 0.05) obtained from the comparison against Day 0. n/s indicates non-significant differences.

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