Daniel Jenkin

Duration of protection from SARS-CoV-2 infection in people living with HIV (PWH) following vaccination is unclear. In a substudy of the phase II/III the COV002 trial (NCT04400838), 54 HIV ⁺ male participants on antiretroviral therapy (undetectable viral loads, CD4 ⁺ T cells > 350 cells/μL) received 2 doses of ChAdOx1 nCoV-19 (AZD1222) 4–6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and Meso Scale Discovery [MSD]), neutralization, ACE-2 inhibition, IFN-γ ELISpot, activation-induced marker (AIM) assay and T cell proliferation. We show that, 6 months after vaccination, the majority of measurable immune responses were greater than prevaccination baseline but with evidence of a decline in both humoral and cell-mediated immunity. There was, however, no significant difference compared with a cohort of HIV-uninfected individuals vaccinated with the same regimen. Responses to the variants of concern were detectable, although they were lower than WT. Preexisting cross-reactive T cell responses to SARS-CoV-2 spike were associated with greater postvaccine immunity and correlated with prior exposure to beta coronaviruses. These data support the ongoing policy to vaccinate PWH against SARS-CoV-2, and they underpin the need for long-term monitoring of responses after vaccination.

Heterologous prime-boost strategies are known to substantially increase immune responses in viral vectored vaccines. Here we report on safety and immunogenicity of the poxvirus Modified Vaccinia Ankara (MVA) vectored vaccine expressing four Mycobacterium avium subspecies paratuberculosis antigens as a single dose or as a booster vaccine following a simian adenovirus (ChAdOx2) prime. We demonstrate that a heterologous prime-boost schedule is well tolerated and induced T-cell immune responses.

Background: A new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19infection in the United Kingdom from November 2020 with a transmission advantage over the previous variants of the virus. Here we report efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19, against this variant in comparison with non-B.1.1.7 lineages. Methods: Volunteers enrolled in phase II/III vaccine efficacy studies in the United Kingdom and randomised 1:1 to receive ChAdOx1 nCoV-19 or a MenACWY control vaccine, providedupper airway swabs every week during the trial and also if they developed possible symptomatic COVID-19 infection. Swabs were tested by nucleic acid amplification test (NAAT) for SARS-CoV-2, and positive samples were sequenced through the COVID-19Genomics UK consortium (COG UK). NAAT data were used to assess the duration ofdetectable viral RNA in diagnostic specimens and the viral load. Anti-spike IgG wasmeasured by ELISA at baseline, 14 and 28 days after prime and 28 days after boostervaccination. Neutralising antibody responses were measured using a live virus neutralisation assay against the B.1.1.7 and Victoria lineages of the virus. The efficacy analysis included symptomatic COVID-19 in seronegative participants with a NAAT positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cut-off on Jan 14, 2021. Vaccine efficacy was calculated as 1 − relative risk derived from a robust Poisson regression model. This study is ongoing and is registered with ClinicalTrials.gov NCT04400838 and ISRCTN 15281137.5 Findings: Between 1st October 2020 and 14th January 2021, 499 participants developed Covid-19infection. 1524 NAAT positive nose/throat swabs were collected from these participants during the trial. Of these, 323 swabs from 256 participants were successfully sequenced.ChAdOx1 nCoV-19 recipients had a significantly lower viral load as represented byminimum PCR Ct value (p<0.0001) and were NAAT positive for a shorter time (p<0.0001) than participants who received the control vaccine. Virus neutralisation activity by vaccineinduced antibodies was 9-fold lower against the B.1.1.7 variant than against a canonical non B.1.1.7 lineage. Vaccine efficacy against symptomatic NAAT positive infection was similar for B.1.1.7 and non-B1.1.7 lineages (74.6% [95%CI 41.6-88.9] and 84% [95% CI 70.7-91.4] respectively). There was no difference in anti-spike antibody titres between individuals who had received a prior ChAdOx1 vectored vaccine and those who were naïve to ChAdOx1. Interpretation: Efficacy of ChAdOx1 nCoV-19 against the B.1.1.7 variant of SARS-CoV-2 is similar to the efficacy of the vaccine against other lineages. Furthermore, vaccination with ChAdOx1 nCoV-19 results in a reduction in the duration of shedding and viral load, which may translate into a material impact on transmission of disease. Trial Registration Number: This study is ongoing and is registered with ClinicalTrials.gov NCT04400838 and ISRCTN 15281137. Funding: The clinical trial was funded by UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR OxfordBiomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome SangerInstitute. Computational work was supported by the Wellcome Trust Core Award Grant Number 203141/Z/16/Z with funding from the NIHR Oxford BRC. Conflict of Interest: Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19. AstraZeneca reviewed the data from the study and the final manuscript before submission, but the authors retained editorial control. SCG is cofounder of Vaccitech (collaborators in the early development of this vaccine candidate) and 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. TL is named as an inventor on a patentapplication covering this SARS-CoV-2 vaccine and was consultant to Vaccitech. PMF is a consultant to Vaccitech. AJP is Chair of the UK Department of Health and Social Care’s JCVI, but does not participate in policy advice on coronavirus vaccines, and is a member of the WHO Strategic Advisory Group of Experts (SAGE). AJP and SNF are NIHR SeniorInvestigators. AVSH is a cofounder of and consultant to Vaccitech and is named as aninventor on a patent covering design and use of ChAdOx1-vectored vaccines(PCT/GB2012/000467). MDS reports grants from Janssen, GlaxoSmithKline, Medimmune,Novavax, and MCM Vaccine and grants and non-financial support from Pfizer outside of the submitted work. CG reports personal fees from the Duke Human Vaccine Institute outside of the submitted work. ADD reports grants and personal fees from AstraZeneca outside of the submitted work. SNF reports grants from Janssen and Valneva, outside the submitted work.TLV and JV are employees of AstraZeneca. All other authors declare no competing interests.The views expressed in this publication are those of the authors and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care. Ethical Approval: The study was sponsored by the University of Oxford (Oxford, UK) and approved in the UK by the Medicines and Healthcare products Regulatory Agency (MHRA) reference 21584/0428/001-0001 and the South-Central Berkshire Research Ethics Committee reference 20/SC/0179.