Study: mRNA Vaccines Fare Better Against COVID Variants

The research adds to growing evidence that mRNA vaccines—like those made by Pfizer and Moderna—offer the best protection.

Concentrated woman doctor vaccinating a young woman
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Fact checked on May 19, 2022 by Vivianna Shields, a journalist and fact-checker.

COVID vaccines that use mRNA technology may provide better protection against WHO-identified variants than viral vector vaccines, new research shows. The findings are in line with what health officials have previously recommended for optimal protection against COVID-19.

The new study, published in PLOS Medicine, sought to compare four vaccines available in the U.S. and U.K.—Pfizer-BioNTech, Moderna, Johnson & Johnson/Janssen, and Oxford-AstraZeneca—and how they perform against five past and present Variants of Concern (Alpha, Beta, Gamma, Delta, and Omicron) identified by the World Health Organization

Although all four vaccines provided protection against severe disease from COVID-19 variants, Pfizer and Moderna's mRNA vaccines provide better overall protection—by way of higher antibody responses after a certain amount of time—than the AstraZeneca and J&J vaccines.

"Based on our results and other current knowledge, vaccination with an mRNA vaccine would, in most cases, lead to a higher immune response and could therefore be preferred," study co-author Jonne Sikkens, MD, PhD, an infectious disease physician at Amsterdam University Medical Centers, told Health.

Here's what to know about the effectiveness of mRNA vaccines on COVID-19 variants, as compared to other available options, and what the research could mean for protection against future virus strains.

mRNA Vaccines Elicit Better Antibody Responses

For the study, researchers from the University of Amsterdam took blood samples from 165 health care workers. For those who took any of the two-dose vaccines (Pfizer, Moderna, and AstraZeneca), samples were taken three and four weeks after the first and second doses, respectively. Blood samples were taken at four to five and eight weeks after vaccination from a single-dose J&J vaccine. Additional samples were taken before and four weeks after a Pfizer booster.

From those samples, researchers measured antibody responses—first, to the original SARS-CoV-2 strain: Samples from participants who received the Moderna vaccine still had the highest antibody responses, followed by samples from Pfizer vaccine participants. Meanwhile, those who received either of the viral vector vaccines had "substantially lower" antibody responses.

A similar scenario played out when testing antibody responses to the variants: neutralizing antibodies were highest following mRNA vaccines as compared to the viral vector vaccines. However, all vaccines still had a reduced ability to neutralize the COVID-19 variants—especially when they were up against Omicron. The Pfizer booster shot was able to substantially improve antibody responses to variants, including Omicron.

Though the findings support previous guidance from the Centers for Disease Control and Prevention (CDC) on choosing mRNA vaccines over other available options, the study still has some limitations. First, the group of participants included more females than males. And regarding the AstraZeneca vaccine specifically, people who received that vaccine were significantly older (in the Netherlands, that vaccine has been restricted to people ages 60 and older), and overall immune responses tend to become weaker with age, study authors said.

More research is also needed to examine the long-term effects of all vaccines on antibody responses, as with other future variants. "Long-term durability of protective effects are still being studied and emergence of new virus variants will lead to a continuously changing situation," said Dr. Sikkens.

Previous Guidance on mRNA vs. Other Vaccines

Recently, public health agencies like the CDC and Food and Drug Administration (FDA) have been urging people to choose mRNA COVID-19 vaccines over the other available option, a J&J vaccine, in the U.S.

In early May, the FDA announced new restrictions on the single-dose J&J vaccine, limiting its use to only people aged 18 or older who are unable or unwilling to receive either mRNA vaccine. Before that, in December 2021, the CDC's Advisory Committee on Immunization Practices preferentially recommended mRNA vaccines; and a few months later in March 2022, the CDC urged people to choose an mRNA booster over an additional J&J shot.

The reasoning for this guidance is twofold: The FDA's restriction of the vaccine is due to an increased risk of a blood clotting issue called thrombosis with thrombocytopenia syndrome (TTS), which has been found to rarely occur following the J&J vaccine. The CDC's urgings also cite the reduced effectiveness of the J&J vaccine as compared to the Pfizer and Moderna options.

Success of mRNA Vaccines Against COVID-19

It's not entirely clear why mRNA vaccines outperform other options, according to study co-author Jonne Sikkens, MD, PhD, an infectious disease physician at Amsterdam University Medical Centers. But researchers have some theories.

The first is simply that the J&J vaccine is a single dose, "which may have limited its effectiveness," Dr. Sikkens told Health, adding that "other research has shown that additional doses of this vaccine increase immune effects."

That other research, as Paul A. Offit, MD, director of the Vaccine Education Center and an attending physician in the Division of Infectious Diseases at Children's Hospital of Philadelphia, points out, shows that a second dose of the J&J vaccine had 94% effectiveness against symptomatic COVID-19 in the U.S.—up from just 66.3% effectiveness from a single dose.

The actual difference in makeup of the vaccines likely plays a role, too, Dr. Sikkens says. The mRNA vaccines encode a portion of the spike protein found on the surface of SARS-CoV-2 to get an immune response, while the viral vector vaccines use an adenovirus which usually causes colds that is modified with the SARS-CoV-2 protein.

Despite the success of mRNA vaccines' antibody responses, its also important to point out that neutralizing antibodies are only one part of immunity. Focusing on only antibody levels "assumes they are a perfect predictor of protection against disease, which isn't true," said Dr. Offit, citing other immunity elements, like memory B cells, which weren't studied in this research. "Neutralizing antibodies can fade to a very low level but you're still protecting against serious illness, which is the goal," said Dr. Offit. "Both types of vaccines meet that goal."

mRNA Vaccines and Protection Against Future Variants

The current research only looks at the antibody responses of vaccines to variants that have already been identified. While it's difficult to say what will happen with future variants, the work here suggests an mRNA booster may be important for maximum protection. "A subsequent boost with an mRNA vaccine can lead to high immune responses against current variants, even against the first Omicron virus type," said Dr. Sikkens.

But a change to the current mRNA vaccines may be even more beneficial. "The Omicron virus has been evolving and several current and future Omicron subtypes may very well be less susceptible to the vaccination-induced immunity of the current vaccines," continued Dr. Sikkens. "Evolvement of current vaccines to incorporate a response specific for these new virus types is becoming more and more important."

For now—until a new or updated vaccine is able to offer more protection against future variants—it's important to keep in mind that, regardless of the vaccine you received, immunization practices are still doing what they were designed to do. "We've confused people about what it means to be fully vaccinated and what matters," said Dr. Offit. "The goal is to protect against serious illness."

The information in this story is accurate as of press time. However, as the situation surrounding COVID-19 continues to evolve, it's possible that some data have changed since publication. While Health is trying to keep our stories as up-to-date as possible, we also encourage readers to stay informed on news and recommendations for their own communities by using the CDC, WHO, and their local public health department as resources.

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