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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335293

ABSTRACT

Background There are no real world data on vaccine elicited neutralising antibody responses for the world’s most widely used vaccine, AZD1222, in African populations following scale up. Here, we measured i) baseline SARS-CoV-2 seroprevalence and levels of protective neutralizing 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 - a period when the Delta variant was 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 (reciprocal dilution of sera required to inhibit 50% of PV infection). Results Our study population receiving 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 ID 50 above the cut-off of 20. In these individuals, binding antibodies to S were also detectable, and neutralisation correlated with IgG anti-S, suggesting waning of N antibody after infection. 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, were not 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. 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 orld 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 low at three months regardless of prior exposure or breakthrough infection. Booster doses after AZD1222 should be considered for those at high risk in the African setting, even after natural infection, as future variants may be more pathogenic as well as immune evasive in the context of waning immunity.

4.
BMJ Glob Health ; 6(3)2021 03.
Article in English | MEDLINE | ID: covidwho-1143036

ABSTRACT

In February 2020, Nigeria faced a potentially catastrophic COVID-19 outbreak due to multiple introductions, high population density in urban slums, prevalence of other infectious diseases and poor health infrastructure. As in other countries, Nigerian policymakers had to make rapid and consequential decisions with limited understanding of transmission dynamics and the efficacy of available control measures. We present an account of the Nigerian COVID-19 response based on co-production of evidence between political decision-makers, health policymakers and academics from Nigerian and foreign institutions, an approach that allowed a multidisciplinary group to collaborate on issues arising in real time. Key aspects of the process were the central role of policymakers in determining priority areas and the coordination of multiple, sometime conflicting inputs from stakeholders to write briefing papers and inform effective national decision making. However, the co-production approach met with some challenges, including limited transparency, bureaucratic obstacles and an overly epidemiological focus on numbers of cases and deaths, arguably to the detriment of addressing social and economic effects of response measures. Larger systemic obstacles included a complex multitiered health system, fragmented decision-making structures and limited funding for implementation. Going forward, Nigeria should strengthen the integration of the national response within existing health decision bodies and implement strategies to mitigate the social and economic impact, particularly on the poorest Nigerians. The co-production of evidence examining the broader public health impact, with synthesis by multidisciplinary teams, is essential to meeting the social and public health challenges posed by the COVID-19 pandemic in Nigeria and other countries.


Subject(s)
COVID-19 , Health Planning , Health Policy , Pandemics , Public Health , Disaster Planning , Humans , Nigeria , SARS-CoV-2
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