The capacity to mount humoral immune responses to COVID-19 vaccinations may be reduced among people who are heavier, older, and male, new findings suggest.
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The data pertain specifically to the mRNA vaccine, BNT162b2, developed by BioNTech and Pfizer. The study was conducted by Italian researchers and was published Feb. 26 as a preprint.
The study involved 248 health care workers who each received two doses of the vaccine. Of the participants, 99.5% developed a humoral immune response after the second dose. Those responses varied by body mass index (BMI), age, and sex.
“The findings imply that female, lean, and young people have an increased capacity to mount humoral immune responses, compared to male, overweight, and older populations,” Raul Pellini, MD, professor at the IRCCS Regina Elena National Cancer Institute, Rome, and colleagues said.
“To our knowledge, this study is the first to analyze Covid-19 vaccine response in correlation to BMI,” they noted.
“Although further studies are needed, this data may have important implications to the development of vaccination strategies for COVID-19, particularly in obese people,” they wrote. If the data are confirmed by larger studies, “giving obese people an extra dose of the vaccine or a higher dose could be options to be evaluated in this population.”
Results contrast with Pfizer trials of vaccine
The BMI finding seemingly contrasts with final data from the phase 3 clinical trial of the vaccine, which were reported in a supplement to an article published Dec. 31, 2020, in the New England Journal of Medicine. In that study, vaccine efficacy did not differ by obesity status.
Akiko Iwasaki, PhD, professor of immunology at the Howard Hughes Medical Institute and an investigator at Yale University, New Haven, Conn., noted that, although the current Italian study showed somewhat lower levels of antibodies in people with obesity, compared with people who did not have obesity, the phase 3 trial found no difference in symptomatic infection rates.
“These results indicate that even with a slightly lower level of antibody induced in obese people, that level was sufficient to protect against symptomatic infection,” Dr. Iwasaki said in an interview.
Indeed, Dr. Pellini and colleagues pointed out that responses to vaccines against influenza, hepatitis B, and rabies are also reduced in those with obesity, compared with lean individuals.
However, they said, it was especially important to study the effectiveness of COVID-19 vaccines in people with obesity, because obesity is a major risk factor for morbidity and mortality in COVID-19.
“The constant state of low-grade inflammation, present in overweight people, can weaken some immune responses, including those launched by T cells, which can directly kill infected cells,” the authors noted.
Findings reported in British newspapers
The findings of the Italian study were widely covered in the lay press in the United Kingdom, with headlines such as “Pfizer Vaccine May Be Less Effective in People With Obesity, Says Study” and “Pfizer Vaccine: Overweight People Might Need Bigger Dose, Italian Study Says.” In tabloid newspapers, some headlines were slightly more stigmatizing.
The reports do stress that the Italian research was published as a preprint and has not been peer reviewed, or “is yet to be scrutinized by fellow scientists.”
Most make the point that there were only 26 people with obesity among the 248 persons in the study.
“We always knew that BMI was an enormous predictor of poor immune response to vaccines, so this paper is definitely interesting, although it is based on a rather small preliminary dataset,” Danny Altmann, PhD, a professor of immunology at Imperial College London, told the Guardian.
“It confirms that having a vaccinated population isn’t synonymous with having an immune population, especially in a country with high obesity, and emphasizes the vital need for long-term immune monitoring programs,” he added.