Kinetics of immune responses to SARS-CoV-2 proteins in individuals with varying severity of infection and following a single dose of the AZD1222

To characterize the IgG and IgA responses to different SARS-CoV-2 proteins, we investigated the antibody responses to SARS-CoV-2 following natural infection and following a single dose of AZD1222 (Covishield), in Sri Lankan individuals. The IgG and IgA responses were assessed to S1, S2, RBD, and N proteins in patients at 4 weeks and 12 weeks since the onset of illness or following vaccination. Antibodies to the receptor-binding domain of SARS-CoV-2 wild type (WT), alpha, beta, and lambda and ACE2 (Angiotensin Converting Enzyme 2) receptor blocking antibodies were also assessed in these cohorts. For those with mild illness and in vaccines, the IgG responses to S1, S2, RBD, and N protein increased from 4 weeks to 12 weeks, while it remained unchanged in those with moderate/severe illness. In the vaccines, IgG antibodies to the S2 subunit had the highest significant rise (P < 0.0001). Vaccines had several-fold lower IgA antibodies to all the SARS-CoV-2 proteins tested than those with natural infection. At 12 weeks, the haemagglutination test (HAT) titres were significantly lower to the alpha in vaccines and significantly lower in those with mild illness and in vaccines to beta and for lambda. No such difference was seen in those with moderate/severe illness. Vaccines had significantly less IgA to SARS-CoV-2, but comparable IgG responses those with natural infection. However, following a single dose vaccines had reduced antibody levels to the VOCs, which further declined with time, suggesting the need to reduce the gap between the two doses, in countries experiencing outbreaks due to VOCs. Those with mild infection, vaccinees (AZD1222) and unexposed individuals had similar antibody levels to S2. Those with mild infection had highest antibody responses to S2, while hose with moderate/severe illness had highest responses to the receptor binding domain. Vaccinees had several fold lower IgA antibodies to all the SARS-CoV-2 proteins tested than those with natural infection.

Automated summary

The study investigated the antibody responses to SARS-CoV-2 in Sri Lankan individuals following natural infection and vaccination with AZD1222. The findings showed that vaccinated individuals had lower IgA antibody levels to SARS-CoV-2 proteins compared to those with natural infection, indicating a need to reduce the gap between vaccine doses in countries experiencing VOC outbreaks.