'Science' Latest Research : Why Does the Flu Vaccine Last Only a Few Months?

Some vaccines make the body's immune response long-term effective. For example, Hepatitis A vaccine can make people immune for life. Other vaccines are only effective for a few months, such as seasonal influenza vaccine that is vaccinated once a year.

This month's 'Science' magazine published the latest research by the Emory University Vaccine Center, revealing why the effects of the flu vaccine can only last for a few months. This discovery is expected to provide a reference for the design of a more durable 'universal' flu vaccine, as well as the current research and development of a new crown vaccine.

Bone marrow is the base of plasma cells that secrete antibodies for a long time. Seasonal influenza vaccination increases the number of influenza-specific plasma cells in the bone marrow, but most of the newly produced cells are gone after a year.

Immune cells produce antibodies, and bone marrow is the base of immune cells. Emory researchers found that seasonal influenza vaccination did increase the number of influenza antibody-producing cells in the bone marrow. However, the vast majority of newly formed cells disappear within a year.
Influenza vaccines need to be injected every year, partly because the influenza viruses that infect humans mutate and exchange genes with viruses in poultry and pigs. At the same time, as this research focuses on, the number of antibodies is declining over time.

Most vaccine studies involve blood samples from subjects — antibody-producing cells can be found in the blood within a few weeks after vaccination.


The research team led by Dr. Rafi Ahmed, director of the Emory Vaccine Center, took a further approach. They collected bone marrow samples from the subjects. Most people inherently have flu-specific plasma cells : an immune cell that secretes large amounts of antibodies. Therefore, researchers need to distinguish between antibodies produced by existing cells and antibodies produced by vaccine stimulation.

Dr. Carl Davis, the first author of the paper and a postdoctoral fellow in Ahmed’s laboratory, said, 'We can track the specific cells produced by the vaccine because they produce unique antibodies that can be identified by sequencing technology.' 'We found that one month after vaccination, the number of new antibodies in the bone marrow increased, but decreased after a year. On the other hand, the number of influenza antibodies that originally existed in the bone marrow remained stable for more than a year.'

Ahmed said, 'This shows that just contacting the bone marrow is not enough. Plasma cells must find a niche in the bone marrow, where they establish a replication mechanism, undergo changes in gene expression and metabolism, so as to improve the sustainability of the immune effect.'

The bone marrow harvesting work was carried out between 2009 and 2018. The collaborator was Edmund K. Waller, a professor at Emory University School of Medicine and Winship Cancer Institute.

53 nos. volunteers agreed to provide bone marrow before and one month after the seasonal flu vaccination, and to follow up approximately one year later. Studies have shown that one month after vaccination, the average proportion of influenza-specific cells increased from 0.8% to 1.9%. However, follow-up a few months later showed that this value had fallen back to the baseline level.

By analyzing the DNA of the cells and detecting the antibodies they produce, the researchers searched for specific antibody-secreting cells stimulated by the vaccine and tracked the degree of enrichment of these cells in the blood and bone marrow. The results showed that 70% to 99% of newly produced antibody cells disappeared after one year.

The good news is that the level of antibody-secreting cells in the blood is related to the long-term response of the bone marrow. Vaccine researchers can continue to monitor the immune response by looking for antibody-secreting cells in the blood.

In addition, Ahmed said that the addition of adjuvant to the vaccine is expected to increase the long-term bone marrow homing of antibody-secreting cells. The adjuvant can also promote the formation of germinal centers, that is, the plasma cell structure in the lymph nodes that produces high-affinity antibodies, thus helping to produce long-lived plasma cells.

The standard inactivated influenza vaccine does not contain adjuvants. The development of suitable adjuvants is a feasible direction to improve the effectiveness of influenza vaccines.