Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in HIV infection: a single-arm substudy of a phase 2/3 clinical trial

Abstract

Background: Data on vaccine immunogenicity against SARS-CoV-2 are needed for the 40 million people globally living with HIV who might have less functional immunity and more associated comorbidities than the general population. We aimed to explore safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine in people with HIV.

Methods: In this single-arm open-label vaccination substudy within the protocol of the larger phase 2/3 trial COV002, adults aged 18-55 years with HIV were enrolled at two HIV clinics in London, UK. Eligible participants were required to be on antiretroviral therapy (ART), with undetectable plasma HIV viral loads (<50 copies per mL), and CD4 counts of more than 350 cells per μL. A prime-boost regimen of ChAdOx1 nCoV-19, with two doses was given 4-6 weeks apart. The primary outcomes for this substudy were safety and reactogenicity of the vaccine, as determined by serious adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and antibody-mediated live virus neutralisation. Cell-mediated immune responses were measured by ex-vivo IFN-γ enzyme-linked immunospot assay (ELISpot) and T-cell proliferation. All outcomes were compared with an HIV-uninfected group from the main COV002 study within the same age group and dosing strategy and are reported until day 56 after prime vaccination. Outcomes were analysed in all participants who received both doses and with available samples. The COV002 study is registered with ClinicalTrials.gov, NCT04400838, and is ongoing.

Findings: Between Nov 5 and Nov 24, 2020, 54 participants with HIV (all male, median age 42·5 years [IQR 37·2-49·8]) were enrolled and received two doses of ChAdOx1 nCoV-19. Median CD4 count at enrolment was 694·0 cells per μL (IQR 573·5-859·5). No serious adverse events occurred. Local and systemic reactions occurring during the first 7 days after prime vaccination included pain at the injection site (26 [49%] of 53 participants with available data), fatigue (25 [47%]), headache (25 [47%]), malaise (18 [34%]), chills (12 [23%]), muscle ache (19 [36%]), joint pain (five [9%]), and nausea (four [8%]), the frequencies of which were similar to the HIV-negative participants. Anti-spike IgG responses by ELISA peaked at day 42 (median 1440 ELISA units [EUs; IQR 704-2728]; n=50) and were sustained until day 56 (median 941 EUs [531-1445]; n=49). We found no correlation between the magnitude of the anti-spike IgG response at day 56 and CD4 cell count (p=0·93) or age (p=0·48). ELISpot and T-cell proliferative responses peaked at day 14 and 28 after prime dose and were sustained to day 56. Compared with participants without HIV, we found no difference in magnitude or persistence of SARS-CoV-2 spike-specific humoral or cellular responses (p>0·05 for all analyses).

Interpretation: In this study of people with HIV, ChAdOx1 nCoV-19 was safe and immunogenic, supporting vaccination for those well controlled on ART.

Funding: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

Figure 1

Solicited local (A) and systemic (B) adverse events in participants vaccinated with ChAdOx1 nCoV-19 Solicited adverse reactions in the first 7 days after vaccination, as recorded in participant symptom electronic diaries. Day 0 is the day of vaccination. Vertical bars show proportion of participants reporting symptoms. Bars are colour-coded to show levels of severity.

Figure 1

Solicited local (A) and systemic (B) adverse events in participants vaccinated with ChAdOx1 nCoV-19 Solicited adverse reactions in the first 7 days after vaccination, as recorded in participant symptom electronic diaries. Day 0 is the day of vaccination. Vertical bars show proportion of participants reporting symptoms. Bars are colour-coded to show levels of severity.

Figure 2

Serological responses to vaccination with ChAdOx1 nCoV-19 in people with HIV SARS-CoV-2 IgG response by standardised ELISA to spike protein in trial participants show individual (A) and grouped (B) responses at days 0, 14, 28, 42, and 56 after vaccination. The threshold for a positive response is shown by the hashed line at 10 EU; horizontal bars show median values. (C) Comparison between HIV-positive and HIV-negative cohorts. Datapoints are medians, with error bars showing 95% CIs. The vertical line at day 28 marks the timing of the booster dose. Plots of anti-spike ELISA on day 56 after vaccination vs CD4 cell count (D) and age (E). Statistics calculated using Spearman's correlation coefficient. Exact numbers of participants who provided data at each timepoint are provided in the appendix (p 3). EU=ELISA units.

Figure 3

Neutralisation of SARS-CoV-2/human/AUS/VIC01/2020 strain (A) Neutralisation of SARS-CoV-2 measured using an FRNT using plasma for 15 randomly selected trial participants with HIV at day 28 boost (blue) and day 56 (orange). Datapoints are mean values at each reciprocal serum dilution. (B) FRNT50 values for the 15 participants at days 0, 28, and 56 after prime vaccination. Undetectable neutralisation is reported as less than 20 FRNT50, and the value 10 was allocated for presentation and analysis. p value calculated using Friedman test. FRNT=focus reduction neutralisation test.

Figure 4

T-cell responses to vaccination with ChAdOx1 nCoV-19 in people living with HIV Time course of IFN-γ ELISpot responses to peptides spanning the SARS-CoV-2 spike vaccine insert for participants with HIV (A) and compared with HIV-negative cohort (B). In panel A, datapoints are readings per participant at each timepoint and the thick horizontal bar shows the median, with error bars showing the IQR; and in panel B, each datapoint is the median of each cohort at each timepoint, with error bars showing the IQR. In panels A and B, the lower limit of detection is indicated with the horizontal dotted line and is set at 48 SFCs per million PBMCs, and vertical dotted lines indicate vaccination timepoints. For panel A, statistical analysis was completed using Wilcoxon signed rank tests and in panel B statistical analysis was completed using Wilcoxon rank sum tests. Frequency of CD4 (C) and CD8 (D) proliferating T cells in response to stimulation by overlapping peptide pools spanning spike S1 and S2. In panels C and D, datapoints represent each participant, and the bars and error bars show the overall median and IQR, and p values were calculated using the Wilcoxon signed rank test. Exact numbers of participants who provided data at each timepoint are provided in the appendix (p 4). ELISpot=enzyme-linked immunospot assay. PBMCs=peripheral blood mononuclear cells. SFC=spot forming cells.