Influenza vaccines can boost immunity, but this improvement is only short-lived. American researchers recently found that immunization increases the levels of antibodies against the seasonal flu-causing virus only for a few months, after which these levels plateau due to the loss of bone marrow plasma cells (BMPC). BMPC are the cells responsible for producing influenza-specific antibodies after vaccination.
How flu vaccines are supposed to work
Because the pathogen is weak to begin with, its introduction is expected to help the body develop immunity without causing any sickness. This process of immunization ensures that the next time the body encounters the same pathogen, its immune response will be swift and even more effective than the first time. The success of most vaccines is due, in part, to pathogen-specific antibody responses.
But according to studies, antibody levels peak in the months following vaccination. They then decline and are maintained at a certain level by non-dividing plasma cells that reside in the bone marrow. These cells, called BMPC, have naturally long lives and produce the majority of immunoglobulin G (IgG) — the most common type of antibody found in circulation — present in the blood of humans.
When a person gets vaccinated, some of his resident BMPC begin producing pathogen-specific antibodies in response to the vaccine. In line with this, several studies have found that the total and pathogen-specific antibody levels of a person correlate closely with the amount of BMPC present in his body.
But recent investigations on the effectiveness of influenza vaccines have reported a rapid decline in protective immunity and antibody levels following vaccination. This observation suggests two possibilities: either flu vaccines fail to induce the desired response from BMPC or the BMPC they elicit fail to become long-lived.
A team led by researchers at the Emory Vaccine Center in Atlanta, Georgia explored these possibilities in a study published last month in the journal Science. (Related: Prestigious vaccine journal: Flu vaccine increases coronavirus infection risk 36%.)
Why flu shots don’t give long-lasting immunity
For their experiment, the researchers examined blood samples from healthy adults who received inactivated influenza vaccines between 2009 and 2018. Besides examining the usual blood samples, they also measured BMPC responses by taking blood marrow samples from the participants before vaccination and one month and one year after vaccination.
The researchers easily detected BMPC that produce influenza-specific antibodies in the bone marrow samples taken from the volunteers prior to vaccination. Twenty-eight days after vaccination, they reported a significant increase in influenza-specific BMPC. The researchers confirmed that this was not inflated by contamination with influenza-specific antibody-secreting cells (ASC), which tend to appear in the blood one week after vaccination.
Before vaccination, influenza-specific ASC were almost undetectable in the blood samples, but they peaked after a week and declined sharply two weeks post-vaccination. On Day 28, the researchers found that ASC levels were once again undetectable. They noted that the magnitude of the ASC response on Day 7 correlated with the rise in influenza-specific BMPC following vaccination.
However, when they looked at bone marrow samples taken a year after vaccination, they found that the number of influenza-specific BMPC declined considerably compared with the amount measured on Day 28. The researchers also observed a similar trend for serum antibody levels.
Based on the level of decline they found in the bone marrow samples, the researchers estimated that the loss of newly generated influenza-specific BMPC occurred within seven months from the time of vaccination. Altogether these findings show that seasonal flu vaccines only boost immunity temporarily, but ultimately fall short of providing the long-term immunity they are designed to give.
“We could see that these new antibodies expanded in the bone marrow one month after vaccination and then contracted after one year. On the other hand, antibodies against influenza that were in the bone marrow before the vaccine was given stayed at a constant level over one year,” said Carl Davis, the study’s lead author and a researcher at the Emory Vaccine Center.
“What this shows,” said Rafi Ahmed, the director of the Emory Vaccine Center and the study’s senior author, “is that just getting to the bone marrow is not enough. A plasma cell has to find a niche within the bone marrow and establish itself there, and undergo gene expression and metabolism changes that promote longevity.”
Ahmed, Davis and their team hope that their study could serve as a reference for other researchers looking to develop longer-lasting “universal” flu vaccines, and contribute to ongoing efforts to develop a vaccine for the Wuhan coronavirus.