Hybrid Immunity in a Mozambican Cohort After 1 or 2 Doses of the BBIBP-CorV Vaccine

Abstract

Background: More than half of the BBIBP-CorV vaccines, outside of Pacific Asia, were distributed in Africa. Nevertheless, there are limited data on the immunogenicity of BBIBP-CorV from Africa. We compared the antibody response, after 1 and 2 doses of the BBIBP-CorV vaccine, in individuals seropositive or seronegative to severe acute respiratory syndrome coronavirus 2 prior to vaccination.

Methods: From March to May 2021, blood samples were obtained at first and second doses of the BBIBP-CorV, and 2 weeks later. Antibody titers against the full-length spike, receptor binding domain and nucleocapsid protein (anti-NC) of severe acute respiratory syndrome coronavirus 2 were measured. Pseudovirus neutralization assays and antibody-dependent cellular cytotoxicity (ADCC) against the D614G, BA.2, and BA.4 variants were also evaluated.

Results: At the second dose, the immunoglobulin G titers for full-length spike and anti-nucleocapsid protein, the ADCC against BA-2, and the neutralizing activity against the D614G and BA.2 were higher in individuals seropositive to any of the epitopes at the first dose (n = 26) compared to the levels observed 2 weeks later in the seronegative group (n = 25). We did not observe an increase on magnitude of binding antibodies, ADCC, and neutralizing activities, in those seropositive, after the second homologous dose of the BBIBP-CorV vaccine.

Conclusions: We suggest that 1 dose of the BBIBP-CorV vaccine in seropositive individuals induced better antibodies response including against variant of concerns compared to that observed after 2 doses in seronegative individuals. A further homologous dose of the BBIBP-CorV vaccine, in those who are seropositive, does not improve the antibody response observed after the first dose.

Keywords: BBIBP-CorV; COVID-19 vaccine; antibodies; hybrid immunity; inactivated vaccine.

Figure 1.

Diagram of the eligibility criteria for selection of participant samples for binding and neutralizing experiments.

Figure 2.

Plasmatic titers of IgG binding antibodies against epitopes of SARS-CoV-2. The median and interquartile ranges of the titers of binding antibodies against the (A) S-region, (B) RBD, and (C) NC region is shown on each graph before the first dose (D0), 21 d after the first dose (D21) and 2 weeks after the second homologous dose (D35) of the BBIBP-CorV vaccine. Each dot represents 1 participant from the seronegative (SN) or seropositive (SP) group. The number of responders on each time point are shown, on each graph, and the cutoff titers for positivity are marked as dot horizontal line on each graph. Significant statistical difference on titers between the time points are showed as *, ***, or **** for P values lower that .05, .001, or .0001, respectively.

Figure 3.

Antibody-dependent cellular cytotoxicity (ADCC) activity against the D614G and Omicron BA.2 and BA.4 sublineages. ADCC activity detected at 21 d after the first dose (D21) and at 2 weeks after the second homologous dose (D35) of the BBIBP-CorV, against (A) the pandemic D614G variant (B) the BA.2 Omicron sublineage and (C) against the BA.4 Omicron sublineage, in seronegative or seropositive participants at time of vaccination. The number of responders on each time point are shown, on each graph, and the cutoff titers for positivity are marked as dot horizontal line on each graph. The median and interquartile ranges of the of ADCC activity against each of the variants, measured as relative light units (RLU), are shown on each graph. Significant statistical difference on RLU between the time points are shown as * or **** for P values lower that .05 or .0001, respectively. D, Number of participants with detectable ADCC activity at D21 and D35 against 1, 2, or the 3 tested variants.

Figure 4.

Plasmatic titers of neutralizing antibodies against SARS-CoV-2 variants at 2 weeks after the second homologous dose of the BBIBP-CorV vaccine. A, Comparison of the neutralizing titers between those seronegative or seropositive participants before the vaccination against the pandemic D614G variant (left) and Omicron BA2 variant (right). The median and interquartile ranges of the of neutralizing titers against each of the variants are shown on each graph. Significant statistical difference on titers between the time points are shown as * or **** for P values lower that .05 or .0001, respectively. The number of responders on each time point are shown, on each graph, and the cutoff titers for positivity are marked as dot horizontal line on each graph. B, Number of participants with detectable neutralizing activity at D21 and D35 against 1 or 2 variants, seropositive and seronegative at baseline visit.