Vaccines that prolong the immune response may provide better protection

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

from Krista Leste-Lasser

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

Vaccination stimulates B cells, a type of immune cell, to produce antibodies against a specific pathogen, such as the flu virus. Most vaccines are designed to produce a rapid and strong immune response lasting a few weeks at most. A few B cells are then stored in the bone marrow as long-lived plasma cells that provide lasting immunity.

But experiments with mice suggest that a longer immune response would theoretically allow the most effective B cells to be recruited as plasma cells.

As immune cells become better at producing specific antibodies, the researchers hypothesized that the body recruited all of its plasma cells from a pool of experienced B cells a few weeks after vaccination.

Consequently, many labs create vaccines that induce a brief, acute immune response, he says David Tarlinton at Monash University in Melbourne, Australia. But that’s based on an idea that’s never been proven, he says.

To test this, Tarlinton and his colleagues vaccinated lab mice with a standard research antigen and then euthanized them a few weeks later to examine the bone marrow in their legs. The mice were genetically modified in a way that created a “time stamp” indicating when B cells were recruited to become plasma cells.

To their surprise, the researchers found that recruitment doesn’t just happen at the end of the immune response, but every day, they say. On average, a new plasma cell is recruited almost every hour after vaccination. The longer the immune response lasted, the more plasma cells ended up in the bone marrow.

“This suggests that the longer you can prolong this immune response, the more antibody-secreting cells you’ll accumulate, and the best ones will be at the end,” says Tarlinton.

That means vaccines may be more effective if they’re designed to induce immune responses that last months rather than weeks, he says. This may involve tweaking the way the vaccine delivers antigens to the body, for example, or adding other substances called adjuvants that modulate the immune response.

For the recipient, the initial inflammation and side effects will be no different than with vaccines that elicit a shorter immune response, Tarlinton says.

Whether plasma cell recruitment works the same way in response to natural infections as opposed to vaccinations remains to be determined, he says.

Journal reference: Science immunology, DOI: 10.1126/sciimmunol.abm8389

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