Allergies and respiratory infections: toward a universal respiratory vaccine?

By Elodie Vaz  | Published on February 23, 2026 | 3 min read

Acute respiratory illnesses—whether viral, bacterial, or allergy-related—remain a major public health challenge. SARS-CoV-2 and other coronaviruses illustrate how quickly viruses can mutate, making regular vaccine updates necessary. Added to this are opportunistic bacteria such as Staphylococcus aureus and Acinetobacter baumannii, common in hospital settings, as well as respiratory allergens like house dust mites, key drivers of allergic asthma.

In a study published on February 19 in Science, Professor Bali Pulendran’s team (Stanford Medicine) describes an intranasal vaccine that, in mice, protects against this heterogeneous set of respiratory threats.

Moving beyond 230 years of antigen-based vaccinology

Since the English physician Edward Jenner, the “vaccinology paradigm for 230 years” has relied on antigenic specificity, Pulendran—professor of microbiology and immunology and the study’s senior author—recalls in a press release. Vaccines mimic a distinctive component of a pathogen in order to induce targeted adaptive immune memory.

But this strategy shows its limits in the face of antigenic drift. “It is becoming increasingly clear that many pathogens can mutate rapidly. Like a leopard changing its spots, a virus can alter the antigens on its surface,” the researcher notes.

While so-called “universal” vaccines have been considered against entire viral families, the idea of a truly cross-cutting vaccine remained marginal. “We were interested in this idea because it seemed a bit outlandish. I don’t think anyone seriously considered that such a thing could be possible,” he says.

Betting on integrated immunity

Rather than targeting an antigen, the vaccine mimics immune signals exchanged during infection. It aims to leverage the interaction between innate and adaptive immunity to establish a prolonged state of pulmonary alert.

“What is remarkable about the innate immune system is that it can protect against a wide array of different microbes,” Pulendran reminds us. Usually transient, this response can nevertheless be prolonged under certain conditions, as suggested by the heterologous effects of the BCG vaccine.

Previous work by the team had shown that lung T cells could sustain activation of innate cells via cytokines that stimulate Toll-like receptors. “These T cells provided an essential signal to maintain activation of the innate immune system, which usually lasts a few days or a week, but in this particular case could last up to three months,” the study’s author explains.

The new vaccine, GLA-3M-052-LS+OVA, combines Toll-like receptor agonists with a model protein (ovalbumin) intended to recruit T cells to the lung, and is administered intranasally.

A “double hit” for pathogens 

In mice, three weekly doses provided at least three months of protection against SARS-CoV-2 and other coronaviruses. Vaccinated animals showed minimal weight loss, a 700-fold reduction in lung viral load, and complete survival.

“The pulmonary immune system is so responsive and vigilant that it can trigger the typical adaptive responses (T cells and virus-specific antibodies) in just three days, which is an extremely short time,” he explains. “Normally, in an unvaccinated mouse, it takes two weeks.”

Protection also extended to bacterial infections with Staphylococcus aureus and Acinetobacter baumannii. Faced with these results, the team broadened its investigation. “So we said to ourselves: ‘What else could get into the lungs?’ (…) Allergens.” When exposed to a house dust mite allergen, vaccinated mice showed an attenuated Th2 response and no mucus hypersecretion.

Toward clinical application?