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 ...

Immunological and clinical efficacy of COVID-19 vaccines in immunocompromised populations: a systematic review

“…The vast majority of included studies evaluated vaccines developed by Pfizer (BNT162b2) or Moderna (mRNA-1273). Thirteen studies included patients who received the vaccine developed by Janssen (Ad26.COV2.S) [ [25] , [26] , [27] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] ], nine included patients vaccinated with the AstraZeneca vaccine (ChAdOx1) [ [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] ], three included patients receiving the CoronaVac vaccine (Sinovac Biotech) [ [50] , [51] , [52] ], and one randomized controlled trial evaluated the vaccine developed by Novavax (NVX-CoV2373) vaccine [ 53 ]. One study included patients receiving the BBV152-Covaxin (Bharat Biotech) vaccine [ 44 ] and one included patients receiving the BBIBP-CorV (Sinopharm) vaccine [ 54 ].…”

“…Most studies assessed anti-SARS-CoV-2 immunity through an immunoassay to detect antibodies targeted at the spike protein, including some targeting specifically the receptor-binding domain (RBD) of the spike protein. Thirty studies reported neutralization assay results in addition to anti-SARS-CoV-2 antibody assays [ 34 , 37 , 41 , 48 , 51 , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] , [79] ]. Thirty-one studies provided data on cellular immunity [ 17 , 21 , 22 , 34 , 37 , 41 , 45 , 46 , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , 72 , [74] , [75] , [76] , [77] , [79] , [80] , [81] , [82] , [83] , [84] ].…”

“…Five studies conducted in people living with HIV found low non-response rates ranging from 0 to 4% [ 48 , 68 , 179 ] (among those, two studies were estimated of good quality in the risk of bias assessment [ 48 , 68 ]) or comparable antibody titres compared to an HIV-negative population [ 41 , 67 ].…”

Humoral response to SARS-CoV-2 vaccines in people living with HIV

“…As a consequence, PLWH were prioritized to receiving anti-SARS-CoV-2 vaccines in many countries. However, while data on the effects of SARS-CoV-2 vaccines in PLWH is increasing, it is still sparse [ 9 , 10 ]. It has been demonstrated before that (for some vaccines) the degree of protection and/or the humoral response in PLWH (children and adults) differs from the one observed in a general population [ 11 , 12 ].…”

SARS-CoV-2 Delta (B.1.617.2) Variant: A Unique T478K Mutation in Receptor Binding Motif (RBM) of Spike Gene

“…So far, 4 different types of COVID-19 vaccines have been introduced to immunize individuals as following: 1) SARS-CoV-2 viral (inactivated) vaccine uses the whole virus to immunize individual after a certain process to kill virus preventing infection ( 30 ); 2) SARS-CoV-2 mRNA vaccine is to deliver the whole codon of S gene mRNA into a cell to express spike protein. The vaccinated individuals generate Abs against foreign spike Ag that eventually protect the individual from SARS-CoV-2 viral infection ( 31 ); 3) SARS-CoV-2 adenovirus vector vaccine is to use adenovirus to deliver the whole codon of S gene into a cell to express spike protein and the mechanism is similar to mRNA vaccine ( 32 33 34 ); 4) SARS-CoV-2 protein vaccine is to use recombinant spike protein prepared using expression systems in various cells, recently insect cells were used to ensure the native conformation expression to immunize individual, which generates Abs against spike protein to protect individual ( 35 36 37 ). The ultimate goal of the COVID-19 vaccine is to generate neutralizing Abs to protect an individual from SARS-CoV-2 viral infection as well as to prevent the spread of SARS-CoV-2 through some differences in method to generate Abs.…”