Results of Com-Cov Mix-and-Match Vaccine Study

January 7, 2022

Earlier last month, results of the Com-Cov2 study were published in The Lancet. The Com-Cov2 study tested the efficacy and safety of mix-and-matching COVID-19 vaccines, including Pfizer, AstraZeneca, Moderna and Novavax. The study included 1,072 participants 50 years of age and older. Exclusionary criteria included “history of confirmed SARS-CoV-2 infection, comorbidities that were considered severe or poorly controlled, anaphylaxis or allergy to a vaccine component, pregnancy, or intent to conceive, breastfeeding, and use of anticoagulants.”

Moderna or Novavax vaccines were administered 8-12 weeks after a first dose of the Pfizer or AstraZeneca vaccine, measuring for IgG antibodies at 28 days after the second dose. IgG antibodies develop during an initial infection, and multiply for several weeks after exposure, eventually plateauing. These antibodies are stored in the body and reproduce if exposed to the same pathogen, forming the basis for long-term protection, and even preventing re-infection.

An AstraZeneca or Pfizer first dose followed by a dose of the Moderna vaccine induced more neutralizing antibodies than two doses of Pfizer or AstraZeneca. Additionally, antibodies induced by a Pfizer first dose and Novavax second dose were higher than antibodies produced after two doses of AstraZeneca, demonstrating “effectiveness of 65–70% against symptomatic SARS-CoV-2 infection and over 90% against hospitalization and death… Strikingly, the Pfizer/ Novavax schedule produced a response below that of all other schedules studied, suggesting important differences in the ability of adenoviral-vectored and mRNA vaccines to prime T cells for subsequent stimulation by protein antigens.” An AstraZeneca first dose followed by a Novavax second dose demonstrated higher levels of neutralizing antibodies and T cells than two doses of AstraZeneca. In fact, T-cell responses across all groups were highest in those who received an AstraZeneca first dose and Novavax second dose.

Participants who received at least one mRNA vaccine dose showed the greatest neutralizing antibody response, generating a greater humoral immune response than two Pfizer vaccines. The highest antibody concentrations were observed in participants who received a Moderna vaccine; this may be due to the fact that the Moderna vaccine dose is 100 micrograms versus a 30 microgram Pfizer vaccine dose.

The authors of this article note that the data does not show “any convincing evidence of additional benefit of mixed schedules in maintaining neutralizing activity against variants of concern,” mainly the delta and beta variant… [additionally,] the T-cell response was maintained across all variants of concern, regardless of schedule.”

Local reactions were observed less frequently in participants vaccinated with the Novavax vaccine. 589 adverse events across 357 participants were recorded, being distributed relatively evenly across the various vaccine groups. “Blood results were taken at enrollment, day 7, and day 28 after boost and graded by modified US Food and Drug Administration toxicity scale. There were no notable differences in biochemical adverse events between groups, with some minor variations reported in white blood cell indices.”

18 participants tested positive for COVID-19 after enrollment, occurring at least two months after a second dose.