More Evidence mRNA Vaccines Fare Better Against COVID’s Many Variants

Immune response against COVID-19 variants of concern (VOCs), including Omicron, was higher following mRNA vaccines than viral vector vaccines, Dutch researchers found.

In a prospective cohort study involving serum samples from 165 healthcare workers naive to SARS-CoV-2, neutralizing antibody responses were higher against examined VOCs a month after vaccination with mRNA vaccines from Pfizer/BioNTech (Comirnaty) and Moderna (Spikevax), reported Marit van Gils, PhD, of the University of Amsterdam, and colleagues.

Moreover, following a booster dose of the Pfizer vaccine, neutralizing antibody titers rose in all vaccine groups, including improved results against Omicron and other World Health Organization-designated VOCs (Alpha, Beta, Gamma, Delta), they wrote in PLoS Medicine.

“Although previous studies have provided valuable initial insights in the sensitivity of VOCs to neutralization induced by infection or vaccination, few studies have directly compared the ability of humoral responses induced by the four different vaccines to cope with VOCs,” van Gils and co-authors wrote.

The FDA recently limited use of Johnson & Johnson’s (J&J) COVID vaccine, though the CDC had already released a preferential recommendation for the Pfizer and Moderna vaccines in December 2021.

The researchers provided a head-to-head comparison of Pfizer-BioNTech, Moderna, J&J, and AstraZeneca, plus a Pfizer booster 5-11 months later against the Alpha, Beta, Gamma, Delta, and Omicron variants.

SARS-CoV-2 negative participants were vaccinated between January and May 2021 with one of the four vaccines, and serum samples were collected 3 weeks after the first dose and 4 weeks after the second for the Pfizer, Moderna, and AstraZeneca vaccines; and 4-5 weeks and 8 weeks after the single-dose J&J shot.

Pfizer boosters were administered between October 2021 and January 2022.

The original cohort included 54 Pfizer, 43 Moderna, 42 AstraZeneca, and 26 J&J recipients. The majority of participants (65%-86%) were women, and most were ages 35-60. However, the AstraZeneca group was mostly adults over age 60 because the Dutch government restricted the vaccine’s use in younger adults, the authors noted.

Overall, all Pfizer and Moderna recipients had a detectable antibody response against the spike protein after one vaccination, while five of 42 AstraZeneca recipients and one of 13 J&J recipients did not.

Examining VOCs, van Gils’ group found that mRNA recipients had higher binding responses versus viral vector vaccines. Not surprisingly, the fold reduction in variant neutralization was largest for Omicron (fold change 0.03, 95% CI 0.02-0.04).

The authors also noted that antibody binding titers against the variants’ spike proteins were “largely unaffected, suggesting that neutralizing antibodies form a minority among all antibodies.”

The authors found a “substantial” proportion of AstraZeneca and J&J recipients without detectable variant neutralization after their initial vaccination series. However, after booster vaccination with the Pfizer vaccine, neutralization titers against Omicron significantly increased, with all participants showing “detectable neutralization titers” against the variant.

“When neutralization activity against the original strain was limited … the capability to potently neutralize different variants is severely diminished,” van Gils and colleagues wrote.

They pointed out that the “neutralization results correlated remarkably well with reported vaccine efficacy of the four vaccines against VOCs … and reinforce the reports that neutralizing antibodies are a strong correlate of protection.”

Limitations to the data include a larger proportion of women versus men, and the fact that the age distribution was not identical in each vaccine group — with more older individuals in the AstraZeneca group — which could affect the results. In addition, the authors did not measure long-term responses post-booster.