Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial

Abstract

Background: People living with HIV are at an increased risk of fatal outcome when admitted to hospital for severe COVID-19 compared with HIV-negative individuals. We aimed to assess safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV and HIV-negative individuals in South Africa.

Methods: In this ongoing, double-blind, placebo-controlled, phase 1B/2A trial (COV005), people with HIV and HIV-negative participants aged 18-65 years were enrolled at seven South African locations and were randomly allocated (1:1) with full allocation concealment to receive a prime-boost regimen of ChAdOx1 nCoV-19, with two doses given 28 days apart. Eligibility criteria for people with HIV included being on antiretroviral therapy for at least 3 months, with a plasma HIV viral load of less than 1000 copies per mL. In this interim analysis, safety and reactogenicity was assessed in all individuals who received at least one dose of ChAdOx1 nCov 19 between enrolment and Jan 15, 2021. Primary immunogenicity analyses included participants who received two doses of trial intervention and were SARS-CoV-2 seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04444674, and the Pan African Clinicals Trials Registry, PACTR202006922165132.

Findings: Between June 24 and Nov 12, 2020, 104 people with HIV and 70 HIV-negative individuals were enrolled. 102 people with HIV (52 vaccine; 50 placebo) and 56 HIV-negative participants (28 vaccine; 28 placebo) received the priming dose, 100 people with HIV (51 vaccine; 49 placebo) and 46 HIV-negative participants (24 vaccine; 22 placebo) received two doses (priming and booster). In participants seronegative for SARS-CoV-2 at baseline, there were 164 adverse events in those with HIV (86 vaccine; 78 placebo) and 237 in HIV-negative participants (95 vaccine; 142 placebo). Of seven serious adverse events, one severe fever in a HIV-negative participant was definitely related to trial intervention and one severely elevated alanine aminotranferase in a participant with HIV was unlikely related; five others were deemed unrelated. One person with HIV died (unlikely related). People with HIV and HIV-negative participants showed vaccine-induced serum IgG responses against wild-type Wuhan-1 Asp614Gly (also known as D614G). For participants seronegative for SARS-CoV-2 antigens at baseline, full-length spike geometric mean concentration (GMC) at day 28 was 163·7 binding antibody units (BAU)/mL (95% CI 89·9-298·1) for people with HIV (n=36) and 112·3 BAU/mL (61·7-204·4) for HIV-negative participants (n=23), with a rising day 42 GMC booster response in both groups. Baseline SARS-CoV-2 seropositive people with HIV demonstrated higher antibody responses after each vaccine dose than did people with HIV who were seronegative at baseline. High-level binding antibody cross-reactivity for the full-length spike and receptor-binding domain of the beta variant (B.1.351) was seen regardless of HIV status. In people with HIV who developed high titre responses, predominantly those who were receptor-binding domain seropositive at enrolment, neutralising activity against beta was retained.

Interpretation: ChAdOx1 nCoV-19 was well tolerated, showing favourable safety and immunogenicity in people with HIV, including heightened immunogenicity in SARS-CoV-2 baseline-seropositive participants. People with HIV showed cross-reactive binding antibodies to the beta variant and Asp614Gly wild-type, and high responders retained neutralisation against beta.

Funding: The Bill & Melinda Gates Foundation, South African Medical Research Council, UK Research and Innovation, UK National Institute for Health Research, and the South African Medical Research Council.

Conflict of interest statement

Declaration of interests Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19 (AZD1222). AstraZeneca reviewed the data from the trial and the final manuscript before submission, but the authors retained editorial control. SCG is cofounder of Vaccitech, a collaborator in the early development of this vaccine candidate, and is named as an inventor on a patent covering use of ChAdOx1-vectored vaccines (PCT/GB2012/000467) and a patent application covering this SARS-CoV-2 vaccine (GB2003670.3). TL is named as an inventor on a patent application covering ChAdOx1 nCoV-19 and was a consultant to Vaccitech. TLV and JV are employees of AstraZeneca. All other authors declare no competing interests.

Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Figures

Figure 1

Study profile, stratified by SARS-CoV-2 serostatus 27 participants (21 HIV-negative people and six people with HIV) were excluded from this interim analysis because of a positive SARS-CoV-2 PCR test within the trial period. Three participants were excluded from the immunogenicity analysis owing to an absence of baseline serology. 12 participants (one withdrawn and 11 positive SARS-CoV-2 PCR tests) did not receive a booster dose. Three participants were excluded from analysis at day 42 as they were lost to follow-up. FLS=full length spike. RBD=receptor-binding domain. *One or more samples were not determined due to insufficient sample volume, haemolysis, or sample not collected.

Figure 2

Solicited local and systemic adverse reactions in the 7 days after priming and booster doses of ChAdOx1 nCoV-19 Day 0 is the day of the priming dose. The severity of adverse events was graded as mild, moderate, or severe.

Figure 3

Immunogenicity to SARS-CoV-2 full-length spike and receptor-binding domain proteins Analyses stratified by HIV status (A) and by SARS-CoV-2 serostatus (B) at baseline in people with HIV. Antibody responses assessed at day 0 (baseline), day 28 (post-priming dose), and day 42 (14 days post-booster dose). Boxes denote interquartile ranges and horizontal bars denote median antibody concentration in BAU/mL. BAU=binding antibody unit.

Figure 4

Correlation of plasma IgG antibody binding to Wuhan-1 Asp614Gly wild-type vs beta (B.1.351) full-length spike protein in vaccine recipients Analyses stratified by day and HIV status. OD=optical density.

Figure 5

Pseudovirus neutralisation responses to Wuhan-1 Asp614Gly wild-type on day 42 in vaccinees Samples below the limit of detection are not shown. Boxes denote interquartile ranges, and horizontal bars denote neutralisation ID50. ID50=inhibitory dilution (50%). RBD=receptor-binding domain.