The WHO has published this
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DRAFT prepared by the SAGE Working Group on COVID-19 vaccines
10 February 2021
5
Background document for the Extraordinary meeting of the Strategic Advisory Group of Experts on
Immunization (SAGE) – 08 February 2021
Pre-clinical studies
Note: The following information is derived from scientific publications. Those publications used the term “ChAdOx1-S (recombinant)” which is equivalent to AZD1222.
The efficacy of ChAdOx1-S (recombinant) was assessed in rhesus macaques. Six animals per group were vaccinated using a prime-only regimen (28 days before challenge) or a prime–boost regimen (56 and 28 days before challenge) intramuscularly with 2.5 × 1010 ChAdOx1-S (recombinant) virus particles each. As a control, six animals were vaccinated via the same route with the same dose of ChAdOx1-S (recombinant) green fluorescent protein (GFP) (one animal was vaccinated 56 and 28 days before challenge and five animals were vaccinated 28 days before challenge). No adverse events were observed after vaccination. Spike-specific antibodies were present as early as 14 days after vaccination and were significantly increased after the second immunization (two-tailed signed-rank Wilcoxon test). Endpoint IgG titres of 400–6,400 (prime) and 400–19,200 (prime–boost) were measured on the day of challenge. Virus-specific neutralizing antibodies were also significantly increased after secondary immunization (two-tailed signed-rank Wilcoxon test) and detectable in all vaccinated animals before challenge (5–40 (prime) and 10–160 (prime–boost)), whereas no virus-specific neutralizing antibodies were detected in control animals. IgM antibodies were present in the serum after vaccination on the day of the challenge in six out of six prime–boost and two out of six prime-only animals SARS-CoV-2 spike-specific T cell responses were detected on the day of challenge by IFNγ ELISpot assay after the stimulation of peripheral blood mononuclear cells with a peptide library that spanned the full length of the spike protein. No statistically significant difference in the magnitude of the response was found between the prime–boost and prime-only group (Mann–Whitney U-test, P = 0.3723). As previously reported6, vaccination with ChAdOx1-S (recombinant) resulted in the induction of neutralizing antibodies against the vaccine vector itself within 28 days of vaccination. Nonetheless, a boost vaccination with ChAdOx1-S (recombinant) resulted in a significant increase in binding and neutralizing antibodies in NHPs and an increase in the SARS-CoV-2 virus-neutralizing titre was not significantly correlated with the ChAdOx1-S (recombinant) virus-neutralizing titre (two-tailed Pearson correlation, r2 = 0.6493 P = 0.0529).
A post-vaccination SARS-CoV-2 challenge in rhesus macaques was conducted to evaluate protection and the potential for vaccine-associated enhanced respiratory disease (VAERD)[2]. Clinical disease score in monkeys was reduced, and the vaccine prevented damage to the lungs. A prime-boost regimen induced humoral immune responses. Viral loads were reduced in the lungs, but there was no reduction in viral shedding from the nose with either prime-only or prime-boost regimens. These suggest that ChAdOx1-S (recombinant) may not prevent infection nor transmission of SARS-CoV-2, but it may reduce illness. The immune responses were not skewed towards a Th2-type and there was no suggestion of enhanced disease following vaccination. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody