Sustained spike-specific IgG antibodies following CoronaVac (Sinovac) vaccination in sub-Saharan Africa, but increased breakthrough infections in baseline spike-naive individuals

Abstract

Introduction: This study investigated the antibody responses to the inactivated COVID-19 vaccine, CoronaVac (Sinovac Biotech) in the African population to provide valuable insights into long-term immunity and breakthrough infections against SARS-CoV-2 in individuals with varying prior IgG seropositivity.

Methods: Real-life cohorts were used to longitudinally track antibody levels against the SARS-CoV-2 spike and nucleoprotein in 60 participants over 12 months to examine the levels of multiple antibody isotypes (S-IgG, S-IgM, S-IgA, N-IgG, and N-IgM).

Results: Throughout the 12 months, we observed consistently high and stable seropositivity rates for spike-IgG antibodies, spike-IgM antibodies showed a decline in frequencies over time, and spike-IgA levels remained moderate and stable. Vaccinated individuals previously positive for spike-IgG antibodies demonstrated strong and persistent seropositivity, while those initially negative experienced a gradual and delayed increase in seropositivity rates. The fold change analysis of S- and N- antibody responses demonstrated a consistently stable and comparable profile over time, indicating that vaccine-induced antibody responses remain constant and lack significant fluctuations beyond the initial boost. The study emphasized that individuals lacking previous IgG positivity showed reduced vaccine-induced spike-IgG antibodies and were more susceptible to breakthrough infections, highlighting their higher vulnerability. All cases of breakthrough infections were asymptomatic, indicating the conferred protection to the vaccinated individuals.

Discussion: The findings corroborated earlier studies on the effectiveness of the CoronaVac vaccine and emphasized the significance of accounting for pre-existing seropositivity in vaccine assessments. This study effectively demonstrated durable antibody responses against SARS-CoV-2 in the African population following the CoronaVac vaccination, providing crucial insights for informing vaccination strategies and safeguarding vulnerable populations. Continuous surveillance is imperative for tracking breakthrough infections and monitoring waning immunity. The insights gained offer crucial direction for public health strategies and enhance comprehension of vaccine effectiveness in sub-Saharan Africa. Further research should explore functional outcomes, cellular immune responses, and the vaccine's effectiveness against different variants to enhance our understanding and optimize vaccine strategies.

Keywords: COVID-19; CoronaVac; antibody concentrations; antibody persistence; breakthrough infections; seropositivity; spike protein; sub-Saharan Africa.

Figure 1

Optical Densities and Concentrations of Spike- and Nucleocapsid-Directed Antibodies Following CoronaVac Vaccination, Stratified by Baseline S-IgG Levels. Figure 1 presents the optical densities (OD) and concentrations of Spike (S) and Nucleocapsid (N) proteins, segmented by subjects with baseline S-IgG positivity and negativity. An unmatched samples Wilcoxon test was employed to assess the differences in OD or concentration between the positive (red) and negative (blue) subjects at specific post-vaccination intervals. The thin, lighter lines represent individual profiles, whereas the bolder, darker lines signify the group’s median. A p-value greater than 0.05 was deemed insignificant (indicated as “ns”; not significant). Statistical significance is denoted by “*” representing a p-value less than 0.05, “**” for a p-value less than 0.01, “***” indicates a p-value less than 0.001, while “****” indicates a p-value less than 0.0001.

Figure 2

Seropositivity of S-and N-directed Antibodies Following CoronaVac Vaccination. Figure 2 summarizes the temporal seroconversion patterns of participants. The horizontal line graphs represent the seropositivity status of each participant at various time points. Each line symbolizes an individual, tracing their shift between positive serostatus (OD antibody response above cut-off, in red) and negative serostatus (OD response below cut-off, in blue).

Figure 3

Boxplots illustrating the concentrations of S-and N-directed antibodies and their corresponding fold changes. Figure 3 shows box plots representing the mean values (dots), medians (horizontal lines), and interquartile ranges (top and bottom of the box) for spike- and nucleoprotein-directed IgG, IgM, and IgA antibody concentrations over time. The x-axis represents the timeline for specimen evaluations, beginning with the baseline (D0), followed by 14- and 28-days post-prime (14PP and 28PP), 28 days post-boost (28PB), and then at intervals of 6-, 9-, and 12-months post-prime (M6PP, M9PP, and M12PP). The y-axis represents concentrations of the respective antibodies in mg/ml Corresponding fold changes in antibody concentrations are visually presented as median fold changes between consecutive time points, with an increase in red shading and a decrease in green shading. The size of the circle corresponds to the magnitude of the change. Insignificance is denoted by p-values greater than 0.05, represented as “ns” (ns; not significant). Statistical significance is indicated by ** (p < 0.01).

Figure 4

Hybrid immunity among the previously exposed group. Figure 4 illustrates the dynamics of antibody responses at various time points in a cohort of 46 individuals who were seropositive for S-IgG+ and 26 individuals with combined seropositivity for S-IgG+ and N-IgG+ at baseline (D0), indicating prior exposure before vaccination. Box plots represent the summarized data of spike-directed IgG antibody OD values and concentrations, including the means (represented by dots), medians (horizontal lines), and interquartile ranges (top and bottom of the box). Additional boxplots display the OD values for S-IgA and N-IgG antibodies. Infections before the full vaccine dose are highlighted as numbers inside grey circles, while breakthroughs defined as infections within two weeks of completing the full dose are indicated as numbers inside black circles. The values enclosed in circles represent absolute numbers. The number of infections is indicated within the corresponding circles, providing insights into the infection patterns and vaccine efficacy. “*” represents a p-value less than 0.05; ns, not significant.

Figure 5

CoronaVac-induced immunity among the previously naive group. Figure 5 showcases the temporal changes in antibody responses among 14 individuals who lacked seropositivity for S-IgG antibodies and 10 individuals who lacked seropositivity for both S-IgG and N-IgG antibodies at baseline (D0), indicating a presumed lack of prior exposure to the antigen before vaccination. Box plots represent the summarized data of spike-directed IgG antibody OD values and concentrations, including the means (represented by dots), medians (horizontal lines), and interquartile ranges (top and bottom of the box). Additional boxplots display the OD values for S-IgA and N-IgG antibodies. Infections before the full vaccine dose are highlighted in pink, while breakthroughs defined as infections within two weeks of completing the full dose are indicated in blue. The number of infections is indicated within the corresponding circles, providing insights into the infection patterns and vaccine efficacy. A p-value greater than 0.05 was deemed insignificant (indicated as “ns”; not significant). Statistical significance is denoted by “*” representing a p-value less than 0.05.