Antibody response in influenza and COVID-19

Abstract

Since 1918, influenza virus has led to four pandemics. In 2020, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 pandemic. Both influenza virus and SARS-CoV-2 continue to cause surges in hospitalizations after the pandemic. The studies in this thesis sought to determine population immunity against these viruses. The risk of influenza was determined by assessing the neutralizing antibody (NAb) titers against the circulating strains just before each influenza season. In 2018 summer, the geometric mean NAb titers (GMT) against a circulating A(H1N1) strain was lower than a strain collected during the prior epidemic, which predicted the dominance of A(H1N1) in the 2018/2019 winter influenza season. In April-June 2019, the GMT against the circulating A(H1N1), A(H3N2) and influenza B viruses significantly decreased, which coincided with the co-circulation of the three influenza subtypes in 2019 summer. Hence, seroprevalence data are helpful in forecasting the dominant strains of the upcoming influenza season. SARS-CoV-2 emerged during the 2019/2020 winter. The newly developed enzyme immunoassay (EIA) and conventional virus neutralization test (cVNT) were used for assessing the antibody response of COVID-19 patients. During the acute phase, immunoglobulin M (IgM) and immunoglobulin G (IgG) against nucleoprotein (N) and spike protein receptor binding domain (RBD) could be detected in most individuals at <14 days post symptom onset (PSO). Although antibody levels declined mainly during the first few months PSO, RBD IgG remained positive in >90% of patients at 12 months PSO. The seroprevalence of COVID-19 in Hong Kong before and during the COVID-19 pandemic, and among Hong Kong residents evacuated from Hubei province in March 2020, were determined. Among the 1938 sera collected in Hong Kong before March 2020, none tested positive for both EIA and cVNT, indicating that SARS-CoV-2 did not circulate in Hong Kong. Among the 452 returnees from Hubei province, 3.3% tested positive with both EIA and cVNT which was much higher than the prevalence of RT-PCR confirmed cases, suggesting that the majority of COVID-19 patients had subclincial infection. As SARS-CoV-2 variants emerged, the risk of these variants to the Hong Kong population was assessed by testing the serum antibody titers of vaccinated or infected individuals. The NAb titers against the Beta, Theta, and Kappa were 3-7 fold lower than those against the ancestral strain. Our mechanistic study showed that RBD with mutation at the amino acid residue 484 affected the antibody binding, indicating that mutation at this site was critical for immune escape. The Omicron variant, which led to the devastating fifth wave in Hong Kong in early 2022, was most immunoevasive, with a >20-fold reduction in serum NAb titers. Our seroprevalence data showed that only <10% of the Hong Kong population had detectable NAb against the Omicron variant before the fifth wave. In particular, none of the older adults aged ≥70 years old had detectable levels of NAb against the Omicron variant. The studies in this thesis illustrated the importance of serological surveillance in determining population immunity. Continual serological surveillance would be crucial in risk assessment, guiding public health measures.