Vaccines that boost the immune system may provide better protection.

An illustration of a B cell that produces antibodies  LIBRARY OF SCIENCE PHOTOS NANOCLUSTERING
An illustration of a B cell that produces antibodies  LIBRARY OF SCIENCE PHOTOS NANOCLUSTERING

Most vaccines are intended to elicit a rapid immune response, but a longer one may allow the most effective immune cells to remain in the bone marrow.

Because of the way certain immune cells are selected for long-term storage, vaccines that elicit a longer immune response may provide longer-lasting protection against infection.

Vaccination stimulates the production of antibodies against a specific pathogen, such as the influenza virus. Most vaccines are designed to elicit a rapid and powerful immune response that lasts only a few weeks at most. Following this, a small number of B cells are stored in the bone marrow as long-lived plasma cells, which provide long-term immunity.

However, mouse experiments suggest that a longer immune response would theoretically allow the most effective B cells to be recruited as plasma cells.

Because immune cells get better at producing specific antibodies over time, researchers assumed that several weeks after vaccination, the body recruited all of its plasma cells from a pool of experienced B cells.

As a result, many laboratories develop vaccines that elicit a brief, sharp immune response, according to David Tarlinton of Monash University in Melbourne, Australia. However, he claims that this is based on an unproven theory.

Tarlinton and his colleagues tested this by immunizing laboratory mice with a standard research antigen and then euthanizing them a few weeks later to study the bone marrow in their legs. The mice had been genetically modified in such a way that a "timestamp" indicating when B cells were recruited to become plasma cells was created.

The researchers were surprised to discover that recruitment occurred not only at the end of the immune response but on a daily basis. A new plasma cell was recruited nearly every hour after vaccination, on average. The greater the duration of the immune response, the more plasma cells were found in the bone marrow.

"This would imply that the longer you can keep this immune response going, the more antibody-secreting cells you'll accumulate, and the best ones will be at the end," Tarlinton says.

This means that vaccines may be more effective if they are designed to elicit immune responses lasting months rather than weeks, he says. This could entail changing the way the vaccine delivers antigens into the body, or adding other substances known as adjuvants that modulate the immune response.

According to Tarlinton, the initial inflammation and side effects for the recipient would be no different than with vaccines that elicit a shorter immune response.

He says it's unclear whether plasma cell recruitment works the same way in response to natural infections as it does in response to vaccinations.

Science Immunology, DOI: 10.1126/sciimmunol.abm8389


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