Safety and immunogenicity of ChAdOx1 nCoV-19 (AZD1222) vaccine in adults in Kenya: a phase 1/2 single-blind, randomised controlled trial

Abstract

Background: There are limited data on the immunogenicity of coronavirus disease 2019 (COVID-19) vaccines in African populations. Here we report the immunogenicity and safety of the ChAdOx1 nCoV-19 (AZD1222) vaccine from a phase 1/2 single-blind, randomised, controlled trial among adults in Kenya conducted as part of the early studies assessing vaccine performance in different geographical settings to inform Emergency Use Authorisation.

Methods: We recruited and randomly assigned (1:1) 400 healthy adults aged ≥18 years in Kenya to receive ChAdOx1 nCoV-19 or control rabies vaccine, each as a two-dose schedule with a 3-month interval. The co-primary outcomes were safety, and immunogenicity assessed using total IgG enzyme-linked immunosorbent assay (ELISA) against SARS-CoV-2 spike protein 28 days after the second vaccination.

Results: Between 28 ^th October 2020 and 19 ^th August 2021, 400 participants were enrolled and assigned to receive ChAdOx1 nCoV-19 (n=200) or rabies vaccine (n=200). Local and systemic adverse events were self-limiting and mild or moderate in nature. Three serious adverse events were reported but these were deemed unrelated to vaccination. The geometric mean anti-spike IgG titres 28 days after second dose vaccination were higher in the ChAdOx1 group (2773 ELISA units [EU], 95% CI 2447, 3142) than in the rabies vaccine group (61 EU, 95% CI 45, 81) and persisted over the 12 months follow-up. We did not identify any symptomatic infections or hospital admissions with respiratory illness and so vaccine efficacy against clinically apparent infection could not be measured. Vaccine efficacy against asymptomatic SARS-CoV-2 infection was 38.4% (95% CI -26.8%, 70.1%; p=0.188).

Conclusions: The safety, immunogenicity and efficacy against asymptomatic infection of ChAdOx1 nCoV-19 among Kenyan adults was similar to that observed elsewhere in the world, but efficacy against symptomatic infection or severe disease could not be measured in this cohort.

Pan-african clinical trials registration: PACTR202005681895696 (11/05/2020).

Keywords: COVID-19; ChAdOx1-nCoV-19; Kenya; vaccine.

Figure 1.. CONSORT diagram.

The per-protocol population comprised randomized participants who had a blood sample at baseline and 28 days after second dose vaccination, and for whom the eligibility criteria were correctly applied. The main reason for withdrawal or not completing vaccination regimen was relocation outside of the study area. One participant died during follow-up, unrelated to vaccination. Ten participants in the rabies group were censored by day 112, additional 9 participants by day 182 and a further 11 participants by day 365.

Figure 2.. Vaccine immunogenicity.

The humoral ( A) and cellular responses ( B) generated by vaccination are shown for trial participants, with blue markers representing the rabies vaccine group and orange the ChAdOx1 nCoV-19 group. Day 0 represents responses at baseline, before the first vaccine dose. For each group, the second dose was administered on Day 84 as shown. Day 112 represents responses measured 28 days after the second vaccination (primary outcome). Data in ( A) represent IgG titres expressed as ELISA units as done for other ChAdOx1 nCoV-19 trials and includes all participants as tabulated in Table 3, with bars representing the geometric mean. Data in ( B) represent interferon-γ ELISpot responses against SARS-CoV-2 spike peptides for the first 40 volunteers enrolled in the trial (20 per vaccine arm), with bars representing the median response. PBMCs – peripheral blood mononuclear cells.