Section 3: Oxford/AstraZeneca Vaccine Shows Promise for Phase 3 Outcomes
With many COVID-19 vaccine being studied and approved for emergency use, one important candidate is the chimpanzee adenovirus-vector (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein.1 The University of Oxford developers of this vaccine have a partnership with AstraZeneca. This Phase 1/2 single-blinded, randomized controlled trial at five sites in the UK compared safety, immunogenicity, and reactogenicity of ChAdOx1 nCoV-19 compared to a meningococcal conjugate vaccine (MenACWY).2 Participants included were between the ages of 18 and 55 years with no history of laboratory-confirmed SARS-CoV-2 or known symptoms were assigned 1:1 to receive either ChAdOx1 nCoV-19 at 5 x 1010 viral particles or a single intramuscular injection of MenACWY. Two of the five sites amended a protocol, thereby permitting the use of prophylactic paracetamol prior to vaccination. Humoral responses were assessed at baseline and follow-up after a single-dose vaccination with a standardized total IgG ELISA against trimeric SARS-CoV-2 spike protein, multiplexed immunoassay, three live SARS-CoV-2 neutralization assays, and a pseudovirus neutralization assay. Cellular responses were assessed at the same timepoints with an ex-vivo interferon-γ enzyme-linked immunospot assay. A total of 1,077 participants were assigned to receive either ChAdOx1 nCoV-19 (n = 153) or MenACWY (n = 534). Safety was assessed over the course of 28 days post-vaccination. Systemic and local reactions were found to be more common in the ChAdOx1 nCoV-19 group compared to the MenACWY group, but were similar to the Pfizer/BioNTech in being primarily composed of transient reactogenicity reactions such as chills, muscle ache, headache, malaise, fever, and pain (p<0.05), that were reduced with prophylactic paracetamol. No serious adverse events were reported with the ChAdOx1 nCoV-19 vaccine. Spike-specific T-cell responses peaked at 14 days (median 856 spot-forming cells/1,000,000 peripheral blood mononuclear cells, IQR 493 to 1802, n = 43). Neutralizing antibody responses were detected in 91% of 35 participants after first dose when measured in MNA80 and 100% of these participants when measured in PRNT50. Anti-spike IgG responses rose at 28 days (median 157 ELISA units [EU], 96 to 317, n = 127) and were further boosted after second dose (639 EU, 360 to 792, n = 10). Overall, ChAdOx1 nCoV-19 was shown to be a safe vaccine that increased antibody responses with potential for positive Phase 3 outcomes.
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