Vaccines that prolong the immune response may give better protection

Most vaccines are designed to provoke a quick immune response, but a longer one might allow the most effective immune cells to stick around in the bone marrow

By Christa Lesté-Lasserre

Vaccines that provoke a lengthier immune response might provide longer-lasting protection against infection, due to the way certain immune cells get selected for long-term storage.

Vaccination spurs B cells, a type of immune cell, to produce antibodies against a specific pathogen, such as the influenza virus. Most vaccines are designed to create a quick and strong immune response, lasting a few weeks at most. After this, a few B cells are stored in the bone marrow as long-lived plasma cells, which provide enduring immunity.

But experiments in mice suggest a lengthier immune response would theoretically allow the most effective B cells to get recruited as plasma cells.

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

Consequently, many laboratories create vaccines that induce a short, sharp immune response, says David Tarlinton at Monash University in Melbourne, Australia. But this is based on an idea that has never been proven, he says.

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

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

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

This means that vaccines might be more effective if they are designed to trigger months-long, rather than weeks-long, immune responses, he says. That could involve adjusting the way the vaccine delivers antigens into the body, for example, or adding other substances called adjuvants that modulate the immune response.

For the recipient, the initial inflammation and side effects would be no different from vaccines that trigger a shorter immune response, says Tarlinton.

Whether plasma cell recruitment works in 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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