Comparative systematic review and meta-analysis of reactogenicity, immunogenicity and efficacy of vaccines against SARS-CoV-2

Abstract

As SARS-CoV-2 vaccines are deployed worldwide, a comparative evaluation is important to underpin decision-making. We here report a systematic literature review and meta-analysis of Phase I/II/III human trials and non-human primates (NHP) studies, comparing reactogenicity, immunogenicity and efficacy across different vaccine platforms for comparative evaluation (updated to March 22, 2021). Twenty-three NHP and 32 human studies are included. Vaccines result in mostly mild, self-limiting adverse events. Highest spike neutralizing antibody (nAb) responses are identified for the mRNA-1273-SARS-CoV and adjuvanted NVX-CoV2373-SARS-CoV-2 vaccines. ChAdOx-SARS-CoV-2 produces the highest T cell ELISpot responses. Pre-existing nAb against vaccine viral vector are identified following AdH-5-SARS-CoV-2 vaccination, halving immunogenicity. The mRNA vaccines depend on boosting to achieve optimal immunogenicity especially in the elderly. BNT162b2, and mRNA-1273 achieve >94%, rAd26/5 > 91% and ChAdOx-SARS-CoV-2 > 66.7% efficacy. Across different vaccine platforms there are trade-offs between antibody binding, functional nAb titers, T cell frequency, reactogenicity and efficacy. Emergence of variants makes rapid mass rollout of high efficacy vaccines essential to reduce any selective advantage.

To mix or not to mix? A rapid systematic review of heterologous prime–boost covid-19 vaccination

“…Furthermore, although there was some consistency between different measurement methods, the diagnostic protocols, measurements, and laboratory equipment used varied in different labs and trials. It might be less accurate to compare the immunogenicity of different studies directly [ 9 ]. Therefore, we did not conduct a meta-analysis to compare the immunogenicity of different vaccine combinations.…”

“…As of late June 2021, there were several approved vaccines available on the market, including BNT162b2 (BNT, messenger RNA platform, mRNA, by Pfizer/BioNTech, Germany), mRNA-1273 (mRNA platform, by Moderna, USA), ChAdOx1 (ChAd, AZD1222, adenovirus vectored platform, by AstraZeneca/Oxford, UK), Janssen/Ad26.COV 2.S (adenovirus vectored platform, by Johnson & Johnson, USA), Sinopharm (inactivated whole-virus vaccine, by Beijing Bio-Institute of Biological Products Co Ltd, China), and Sinovac-CoronaVac (inactivated whole-virus vaccine, by Beijing-based pharmaceutical company Sinovac, China), etc [ 2 ]. The premarket efficacy was good, and postmarketing surveillance also showed robust effectiveness [ 9 ]. According to the vaccine instructions and clinical trial design, two doses are required to ensure adequate protection for most of these vaccines, and the prime–boost interval ranged from 21 days to 3 months.…”

Safety and Reactogenicity of the ChAdOx1 (AZD1222) COVID-19 Vaccine in Saudi Arabia

“…The most prevalent systemic symptoms included: fever, chills, headache, myalgia, and fatigue as documented in a meta-analysis of all COVID-19 vaccines (McDonald et al, 2021). The administration of COVID-19 vaccination could be homologous (the first and second doses are of the same vaccine) or heterologous (different vaccines for the first and the second dose).…”

Interpreting estimates of coronavirus disease 2019 (COVID-19) vaccine efficacy and effectiveness to inform simulation studies of vaccine impact: a systematic review

“…Second, in the absence of data, we assume that efficacies against symptomatic disease and infection are the same 45,46 . Third, for the AstraZeneca vaccine, immunogenicity data shows no significant boosting effect from the second dose 47,48 . Furthermore, efficacy after the first AstraZeneca dose against symptomatic disease was not significantly different to efficacy after the second dose in clinical trials 47 .…”