SARS-COV-2 antibody responses to AZD1222 vaccination in West Africa

Abstract

Real-world data on vaccine-elicited neutralising antibody responses for two-dose AZD1222 in African populations are limited. We assessed baseline SARS-CoV-2 seroprevalence and levels of protective neutralizing antibodies prior to vaccination rollout using binding antibodies analysis coupled with pseudotyped virus neutralisation assays in two cohorts from West Africa: Nigerian healthcare workers (n = 140) and a Ghanaian community cohort (n = 527) pre and post vaccination. We found 44 and 28% of pre-vaccination participants showed IgG anti-N positivity, increasing to 59 and 39% respectively with anti-receptor binding domain (RBD) IgG-specific antibodies. Previous IgG anti-N positivity significantly increased post two-dose neutralizing antibody titres in both populations. Serological evidence of breakthrough infection was observed in 8/49 (16%). Neutralising antibodies were observed to wane in both populations, especially in anti-N negative participants with an observed waning rate of 20% highlighting the need for a combination of additional markers to characterise previous infection. We conclude that AZD1222 is immunogenic in two independent West African cohorts with high background seroprevalence and incidence of breakthrough infection in 2021. Waning titres post second dose indicates the need for booster dosing after AZD1222 in the African setting despite hybrid immunity from previous infection.

Fig. 1. Study sites and design.

a Map of Western Africa showing study sites in Ghana and Nigeria. Study design and flow of patient disposition for recipients of AZD1222 two dose in (b) Lagos, Nigeria and (c) Kumasi, Ghana cohorts.

Fig. 2. Longitudinal SARS-CoV-2 neutralization by sera from AZD1222 vaccinated individuals in two west African countries.

a Plasma neutralization of pseudovirus after two doses of the AZD1222 from Nigerian participants at three consecutive time points: baseline (prior to first-dose vaccination), 1 mth after 2^nd dose vaccination and 3 mth after vaccination (n = 49). b Plasma neutralization of pseudovirus after two doses of the AZD1222 from Ghanaian participants at two consecutive time points: baseline (prior to first-dose vaccination) and 1 mth after 2nd dose vaccination (n = 45). Data are representative of two independent experiments comprising of two technical replicates. c Plasma neutralization of pseudotyped virus after two doses of the AZD1222 vaccine against VOC from (n = 15) Nigerian participants at baseline (prior to 1st dose vaccination), 1m (1 month) after 2nd dose vaccination and 3m (3 months) after vaccination and were anti-N IgG negative throughout study period. d Plasma neutralization of pseudotyped virus after two doses of the AZD1222 vaccine against VOC from (n = 32) in Ghanaian participants at baseline (prior to 1st dose vaccination) and 1m (1 month) after 2nd dose vaccination and were anti-N IgG negative throughout study period. Data points were compared using Wilcoxon test and shown as geometric mean titre (GMT) with 95% CI. Data are representative of two independent experiments comprising of two technical replicates. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; ns = not significant.

Fig. 3. Longitudinal SARS-CoV-2 neutralization by sera from AZD1222 vaccinated individuals in two west African countries stratified by N antibody status at baseline.

a Neutralisation titres before and after vaccine (n = 49) stratified by N antibodies at baseline in Nigerian participants. b Neutralisation titres before and after vaccine (n = 45) stratified by N antibodies at baseline in Ghanaian participants. Data points were compared using Wilcoxon test and shown as geometric mean titre (GMT) with 95% CI. Data are representative of two independent experiments comprising of two technical replicates. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001; ns = not significant.

Fig. 4. Kinetics of anti-SARS-COV-2-IgG antibodies in eight participants with evidence of breakthrough infection in the Nigerian cohort.

a–g including one (h) with evidence of breakthrough infection and re-infection with SARS-COV-2 reinfection following evidence of positive IgG anti-N at baseline; negative IgG anti-N at 1 month after second dose and positive IgG anti-N 3 months post-second dose. Binding antibodies to Wu-1 and Omicron BA.1 are shown.

Fig. 5. Neutralising and binding SARS-CoV-2 antibody responses one and 3 months after vaccination in context of breakthrough in the Nigerian cohort.

a Serum neutralization against pseudotyped virus from individuals with vaccine breakthrough occurring between months 1 and 3 post second dose and with no evidence of previous infection prior to vaccine (n = 8, N antibody +ve), and those without breakthrough or past infection prior to vaccine (n = 15, N antibody −ve). b Total anti-spike binding IgG levels in individuals with breakthrough infection between 1 and 3 months post vaccination (n = 8) and with no evidence of ‘natural’ infection (n = 15). Data points were compared using Wilcoxon test and shown as geometric mean titre (GMT) with 95% CI. Data are representative of two independent experiments comprising of two technical replicates. *P < 0.05.