A smarter shot: Scientists explore single-dose vaccine power

A potential single-dose vaccine might be closer than we think. Scientists say it could one day protect against viruses like HIV or COVID-19 without the need for repeat shots.

The secret? Pairing two immune-boosting ingredients – called adjuvants – in the same formula.

In a recent study with mice, researchers from the Massachusetts Institute of Technology (MIT) and the Scripps Research Institute showed how this dual-adjuvant strategy triggered a much broader immune response than standard vaccines.

The mix helped the body produce a wider variety of antibodies, offering stronger, longer-lasting protection from infection.

Adjuvants matter in single-dose vaccines

Adjuvants are added to many vaccines to help fire up the immune system. They don’t act on the virus directly, but they do help your body learn to recognize and fight it.

One common adjuvant is alum (aluminum hydroxide), and it is used in vaccines for hepatitis A and B. It boosts the immune system by activating the body’s first line of defense.

Years ago, scientists at Scripps created another adjuvant using saponin, a compound from the bark of the Chilean soapbark tree.

This adjuvant, when packaged into tiny particles, along with another immune stimulator (MPLA), showed even better results.

That combo, known as SMNP, is already being tested in an HIV vaccine in human trials.

The team decided to test what would happen if they combined alum and SMNP in a single-dose vaccine. The result? An even more powerful immune response against both HIV and SARS-CoV-2.

Single-dose vaccine sticks around

For the new study, researchers focused on how these two adjuvants work together. They used a protein from HIV called MD39 as their target and stuck dozens of these proteins to alum particles, along with SMNP.

When injected into mice, this enhanced vaccine headed straight for the lymph nodes. These small structures are where immune cells, like B cells, train to recognize invaders.

Inside the lymph nodes, B cells mutate rapidly to make stronger, more precise antibodies. This training happens in special clusters called germinal centers.

The scientists found that their vaccine was able to slip through the protective shell around the lymph nodes and stay intact. It remained inside for almost a month – a long time in immune system terms. That allowed B cells to keep working and improving their antibody response.

“As a result, the B cells that are cycling in the lymph nodes are constantly being exposed to the antigen over that time period, and they get the chance to refine their solution to the antigen,” said J. Christopher Love, the Raymond A. and Helen E. St. Laurent Professor of Chemical Engineering at MIT.

Wider arsenal of antibodies

To understand the impact, the team used single-cell RNA sequencing to analyze the B cells from the vaccinated mice.

The group that received both adjuvants in a single-dose vaccine showed a much more diverse set of B cells and antibodies.

They had two to three times more unique B cells than mice that got just one adjuvant.

That matters. The more diverse the antibodies, the better the chances of being effective against different strains of a virus, like HIV, that mutates constantly.

“When you think about the immune system sampling all of the possible solutions, the more chances we give it to identify an effective solution, the better,” Love explained.

“Generating broadly neutralizing antibodies is something that likely requires both the kind of approach that we showed here, to get that strong and diversified response, as well as antigen design to get the right part of the immunogen shown,” he added.

Toward a one-and-done vaccine

This approach could simplify vaccine schedules. Instead of needing multiple doses, a single shot might be enough.

“What’s potentially powerful about this approach is that you can achieve long-term exposures based on a combination of adjuvants that are already reasonably well-understood, so it doesn’t require a different technology. It’s just combining features of these adjuvants to enable low-dose or potentially even single-dose treatments,” Love concluded.

The research points to a future of smarter vaccines – and fewer needles.

The full study was published in the journal Science Translational Medicine.

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