Antibody responses to AZD1222 vaccination in West Africa (preprint)

ABSTRACT

Background: There are no data on vaccine elicited neutralising antibody responses for the most widely used vaccine, AZD1222, in African populations following scale up. Here, we measured i. baseline SARS-CoV-2 seroprevalence and levels of protective antibodies prior to vaccination rollout using both flow cytometric based analysis of binding antibodies to nucleocapsid (N), coupled with virus neutralisation approaches and ii. neutralizing antibody responses to VOC prior to vaccination (January 2021) and after two-doses of AZD1222 vaccine administered between June and July 2021 in Lagos, Nigeria, during a period when the Delta variant was also circulating. Methods: Health workers at multiple sites in Lagos were recruited to the study. For binding antibody measurement, IgG antibodies against SARS-COV-2 Wuhan-1 receptor-binding domain (RBD), trimeric spike protein (S), nucleocapsid protein (N) and Omicron S1 were measured using the Luminex-based SARS-CoV-2-IgG assay by flow cytometry. For plasma neutralising antibody measurement, SARS-CoV-2 lentiviral pseudovirus (PV) were prepared by transfecting 293T cells with Wuhan-614G wild type (WT), B.1.617.2 (Delta) and BA.1 (Omicron) plasmids in conjunction with HIV-1 expression vectors and luciferase encoding genome flanked by LTRs. We performed serial plasma dilutions from each time point and mixed plasma with PV before infecting HeLa-ACE2 cell lines, reading out luminescence and calculating ID50 (dilution of sera required to inhibit 50% of PV infection). Results: Our study population who received at least one dose of vaccine comprised 140 participants with a median age of 40 (interquartile range 33, 48). 62/140 (44%) participants were anti-N IgG positive prior to administration of first vaccine dose. 49 had plasma samples available at baseline prior to vaccination and at two follow-up timepoints post vaccination for neutralization assays. Half of the participants, 25/49 (51%) were IgG anti-N positive at baseline. Of the 24 individuals anti-N Ab negative at baseline, 12/24 had ID50 above the cut-off of 20. In these individuals, binding antibodies to S were also detectable, and neutralisation correlated with IgG anti-S. Overall, neutralizing Ab titres to WT 1 month after second dose were 2579 and at 3 months post second-dose were 1695. As expected, lower levels of neutralization were observed against the Delta GMT 549 and Omicron variants 269 at 1 month. Positive anti-N IgG Ab status at baseline was associated with significantly higher titres of neutralizing antibodies following vaccination across all tested VOC. Those with anti-N Abs present at baseline did not experience waning of responses between months 1 and 3 post second dose. When data were analysed for negative anti-N IgG status at any timepoint, there was a significant decline in neutralization and binding antibodies between 1 month and 3 months post second-dose. The GMT in these individuals for Delta and Omicron was approximately 100, nearly a log lower in comparison to WT. We tested anti-N IgG in subjects who were anti-N IgG negative at baseline (n=78) and became positive between 1- and 3-months post second dose and found 7/49 (14%) with de-novo infection, with one additional participant demonstrating both reinfection and breakthrough infection to yield a total breakthrough rate of 8/49 (16%). Neutralising and binding Ab titres 1 month post vaccine, prior to breakthrough, did not appear to be associated with breakthrough infection. Neutralizing titres were higher at the last time point in individuals who had experienced vaccine breakthrough infection (with no evidence of infection prior to vaccine), indicating a boosting effect of infection in addition to vaccine. We noted that the increase in titres against Delta PV observed in breakthrough was significantly greater than the increase for WT and Omicron PVs, coincident with in the Delta wave of infection during the sampling period. Conclusions: AZD1222 is immunogenic in this real world west African cohort with significant background seroprevalence and incidence of breakthrough infection over a short time period. Prior infection and breakthrough infection induced higher anti-SARS-CoV-2 Ab responses at 3 months post vaccine against all widely circulating VOC. However, responses to Omicron BA.1 were reduced at three months regardless of prior exposure. Given that data suggesting that mRNA vaccine booster third doses induce broader, more potent responses with reduced mortality in the elderly, further doses after AZD1222 should be considered for those at high risk.