SARS-CoV-2 Antibody Responses to AZD1222 Vaccination in West Africa

Abstract

There is a paucity of real-world data on vaccine elicited neutralising antibody responses for AZD1222, in African populations following vaccination scale up. Here, we first measured baseline SARS-CoV-2 seroprevalence and levels of protective neutralizing antibodies prior to vaccination rollout using both flow cytometric based analysis of binding antibodies coupled with pseudotyped virus neutralisation assays in two study cohorts from West Africa: Nigerian healthcare workers; (n = 140) and a Ghanaian general community cohort (n = 527). We found that 44% and 28% of pre-vaccination participants showed IgG anti-N positivity, increasing to 59% and 42% respectively with anti-receptor binding dominan (RBD) IgG specific antibodies. The increased prevalence of prior exposure using anti RBD antibodies was corroborated by Pseudotyped virus (PV) neutralizing antibody assays, indicating that overall, 50% of prior infections were missed by N antibody testing. PV titres (serum dilution required to inhibit 50% of infection, ID50) against wild type following 2-dose vaccination regimen were [145 (4.5) to 2579 (4.2) vs 57 (3.0) to 1049 (6.7)] (GMT ± s.d), delta [75 (3.0) to 549 (3.7) vs 37 (2.4) to 453 (7.4)] (GMT ± s.d) and omicron variants [37 (2.4) to 453 (7.4) vs 29 (1.8) to 95 (5.3)] (GMT ± s.d) in the Nigerian (1 month) vs Ghanaian participants (2 months) post vaccination (total n = 94). Previous IgG anti-N was associated with significantly higher neutralizing antibody levels with an observed 3.5-fold [1423 (3.9) vs 4674 (3.4)] (GMT ± s.d) and 2.7-fold [779 (7.1) vs 2128 (4.8) (GMT ± s.d) difference between N positive and negative participants in the Nigerian and Ghanaian cohorts respectively. We also observed serological evidence from N, S and RBD antibodies of breakthrough infection in 8/49 (16%) of Nigerian vaccinees over only 2 months, with neutralisation profiles suggesting delta variant infection consistent with the sampling period when this variant was known to dominate. Importantly, neutralising antibodies waned at 3 months after second dose vs 1 month post second-dose 1695 (4.3)] vs 2579 (4.2) in the Nigerian population who were N negative throughout. IgG anti-N was also observed to wane below cut-off in a total 19/94 (20%) of subjects highlighting the need for a combination of additional markers to characterise previous infection. We conclude that AZD1222 is immunogenic in two independent real world West African cohorts with high background seroprevalence and incidence of breakthrough infection in 2021. Waning titres at 6 months post second dose indicates the need for booster dosing after AZD1222 in the African setting despite hybrid immunity from previous infection.

West African pre-pandemic cross-reactive antibody and cellular responses against SARS-CoV-2

“…In the past, we have used LFn to study T cell responses against several viruses, including HIV, Ebola, Zika, dengue, and SARS-CoV-2. [22][23][24]18 In our SARS-CoV-2 study of Nigerian HCWs and individuals from the general population, among individuals with SARS-CoV-2 N-only antibodies prior to vaccination, suggestive of prior exposure to hCoV, 81.8% (9/11) had T cell responses to SARS-CoV-2 N. These results provided further evidence that individuals who were previously exposed to hCoVs could have cross-reactive cellular responses against SARS-CoV-2.…”

“…Pseudotype virus neutralization assay was performed on Hela-ACE2 cells using SARS-CoV-2 spike pseudotype virus (PV) expressing luciferase as previously described. 23,24 Briefly, dried plasma spots were eluted and heat inactivated at 54°C for 1 hour, 25 and incubated with PVs at 37°C for 1 hour prior to addition of Hela-ACE2 cells. The plasma dilution/virus mix was incubated for 48 hours in a 5% CO2 environment at 37°C, and luminescence was measured using the Bright-Glo Luciferase assay system (Promega UK, United Kingdom).…”