One Paper A Day: Reviewing clinical paper "Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial"

15 Jul 2021 Categorised under:  OPAD

TLDR

This paper describes the efficacy of preventing COVID-19 disease by mixing the Astra Zeneca vaccine with the Pfizer BioNTech vaccine across the first and booster doses of COVID-19 vaccination. Paper can be found here

Why should you be interested in this paper?

• To end the current ongoing COVID-19 pandemic, it is paramount that we increase vaccination rates globally. However, vaccination campaigns could be limited by vaccine manufacturing, logistics, safety halts, geopolitics, etc. Therefore, having varied vaccination combinations would be most helpful in eliminating some of these limitations by ensuring flexibility in innoculation.
• Additionally, emerging literature suggest that mixing of vaccination types across the first dose and the booster dose can potentially improve immunogenecity and, thus, vaccine efficacy.
• With emerging variants of concern for COVID-19, this approach has potential to provide greater protection coverage since different vaccine types are developed for different variants or parts of COVID-19 (e.g. spike protein vs inactivated virus).

Key learning points

Methods

• Study design and characteristics: CombiVacS is a phase 2, multicentre, open-label, randomised, controlled trial done at five university hospitals in Spain. Hypothesis was that immunogenicity after Pfizer vaccination would be superior to no vaccination in patients who was primed with one dose of Astra Zeneca vaccination. Patients who had previous COVID infections or had a second dose of vaccination (regardless of manufacturer) were excluded from the study.
• Randomisation and masking: Participants were randomly assigned (2:1) to receive one intramuscular injection of BNT162b2 or maintain observation.
• Procedures: Participants were monitored on day 0, 7 and 14 for adverse effects from vaccination. Additionally, blood samples were drawn at these visits for safety and immunology monitoring purposes.
• Outcomes: Humoral immune resposnse to vaccination was anlysed at D14 after vaccination: (1) Antibodies against SARS-CoV-2 spike protein titers. (2) Secondary immunogencity outcome of neutralising antibodies titers. (3) Inflammatory IFN-gamma cytokien production against SARS-CoV-2 spike protein.

Results

• Geometric mean titers of antibodies specific to SARS-CoV-2 receptor binding domain in the intervention group (7756.68) compared to the control group (99.84), 14 days after 2nd dose of vaccination. Immunogenic response in the intervention group (4353.51) compared to the control group (90.05), 7 days after 2nd dose of vaccination.
• Geometric mean titers of antibodies specific to SARS-CoV-2 spike protein in the intervention group (3684.87) compared to the control group (101.2) 14 days after 2nd dose of vaccination. Response in the intervention group (2246.25) compared to control group (102.5) 7 days after the vaccination.
• Similar to other studies known, this study also found better immune responses to vaccination with longer intervals between first and second dose of vaccinations. The same can be said for the side effect profile as well.
• Adverse reactions to vaccination were more common amongst women as compared to men. Interestingly, women also has a stronger immune response to vaccines compared to men. Thromboembolic events are more common with the Astra Zaneca vaccine. Anaphylaxis events are more common with the Pfizer vaccine.

Thoughts

• Promising uncomplete study with more upcoming findings in the future on the possibility of hterologous vaccination schedules.
• Limitation of control arm not having homologous vaccinations. This was because the Astra Zeneca vaccination was suspended for use in the country of study, Spain.
• Another limitation is the relatively smaller sample size. However, as the study is ongoing, future research might reveal more convincing results.