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Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses

Our take —

Less reactogenicity was experienced after the booster dose of ChAdOx1 vaccine (developed by Oxford & AstraZeneca) compared to the initial dose of the vaccine, independent of dose interval. This is the opposite of what has been found for other mRNA vaccines. The authors posit investigation of schedules mixing vaccine technologies to reduce overall instances of reactogenicity. Overall, the ChAdOx1 vaccine was well tolerated in a two-dose regimen. Multifunctional antibody responses and T-cell responses that were induced by the initial vaccine dose were enhanced by a booster dose. The two-dose regimen is currently being evaluated in phase 3 trials. Additionally, this vaccine has received Emergency Use Authorization in the UK as well as several other countries, but not yet in the US.

Study design

Randomized Controlled Trial

Study population and setting

Participants between the ages of 18 and 55 years were recruited between April 23 and May 21, 2020. 52 participants who had already received one dose of the ChAdOx1 vaccine were boosted with a second dose of vaccine 56 days later, with 10 receiving control MenACWY vaccine instead. A “dose-sparing” half dose was also tested on day 56. Data on participants receiving a booster dose 28 days after the initial dose was previously reported and was reproduced in this paper for comparison between booster strategies. Adverse events, anti-spike antibody titers, T-cell responses and cytokine production were analyzed.

Summary of Main Findings

The booster dose of the ChAdOx1 vaccine resulted in minimal side effects, less than the initial dose. This was consistent for all booster regimens, and no serious adverse events were reported. Neutralizing antibody titers increased after the initial dose, with an even further increase following the booster dose. However, a half dose booster resulted in lower antibody titers than the others. Antibody-dependent phagocytosis was induced by the initial dose and enhanced by booster doses, more so with 56-day interval booster. Complement deposition also increased. Similar increases in anti-spike IgM, IgG, and IgA antibodies were achieved for all boost strategies. Anti-spike IgG levels were similar to that in convalescent plasma by day 14, though no correlate of protection has been identified so the relevance of these antibody levels is unclear. No significant increase in spike-specific T-cells was seen following any of the booster doses. The anti-vector immune response slightly increased following booster consistently across groups but did affect anti-spike immune response. No correlation between pre-existing anti-vector immunity and side effects after booster was found.

Study Strengths

This study compared results from their participants to serum samples from a cohort of 21 convalescent serum donors. They also tested multiple booster dosing schedules as well as doses, taking into consideration the possibility of dose-sparing.

Limitations

Participants were limited to ages 18 to 55 years, excluding vulnerable elderly populations. The cohort size for this study was also small. Finally, true correlates of protection against SARS-CoV-2 are still unknown.

Value added

A description of the immune response after different booster doses and schedules using the ChAdOx1 vaccine.

This review was posted on: 14 January 2021