From injection to ingestion: Can yeast make vaccines more accessible?

HN Summary

• Oral Yeast-Based Vaccines: Researchers, including Emilija Vasiliunaité at Vilnius University Life Sciences Center, are developing vaccines using genetically modified yeast, which produce viral antigens and can potentially be ingested rather than injected, making immunization more accessible, affordable, and acceptable.

• Mechanism and Evidence: Yeast cells protect antigens from stomach acid and may act as natural immune stimulants; experiments in mice and preliminary human trials (e.g., “beer vaccines”) show immune responses, demonstrating proof-of-principle for edible vaccines, though further research is needed.

• Implications and Challenges: Oral vaccines could reduce psychological and logistical barriers, simplify production, and increase coverage, but regulatory hurdles, safety testing, and understanding the immune mechanisms remain critical before widespread use.

The idea of consuming a vaccine rather than receiving it by injection may sound implausible. Yet together with colleagues at the Vilnius University Life Sciences Center and collaborators from the National Cancer Institute in the United States, we are exploring yeast-based oral vaccines as a potential way to make immunisation more accessible, affordable, and acceptable worldwide. Our research raises broader questions about how vaccines could be produced and delivered in the future.

Is injection the only way to vaccinate?

In recent years, the scientific community has increasingly recognised that even when effective and safe vaccines exist, accessibility often remains insufficient. This became especially evident during the COVID-19 pandemic. Although mRNA technology enabled vaccine development at unprecedented speed, production and distribution required complex infrastructure, including ultra-low storage temperatures. In some parts of the world, these requirements became major obstacles.

At the same time, vaccination coverage has been declining in many countries. Even a growing body of safety and efficacy data has not fully reversed this trend. The reasons are varied: fear of needles, scepticism toward the pharmaceutical industry, and fatigue from intensive vaccination schedules — particularly in infancy.

As both a researcher and the mother of a young baby, I have personally experienced how emotionally demanding infant vaccination visits can be for parents. Interestingly, orally administered vaccines, such as the rotavirus vaccine that babies often sip willingly, tend to feel less distressing than injectable vaccines that may require multiple injections during a single appointment.

For these reasons, attention is increasingly turning to edible or oral vaccine formats. Such vaccines could potentially reduce psychological barriers and simplify manufacturing. If a vaccine were perceived more like a food product or dietary supplement than a medical injection, production might be more flexible and less costly. Importantly, there would be no need for extensive antigen purification, as is required for traditional injectable vaccines.

Yeasts – unexpected allies in vaccine development

In our joint work between Vilnius University Life Sciences Center and the National Cancer Institute, we adapted a genetic engineering approach previously developed at our centre. We introduce circular DNA molecules into yeast cells, encoding a target viral antigen. In simple terms, we provide the yeast with a “recipe,” enabling it to produce the desired viral protein itself. The genetically modified yeast cell then becomes a kind of vaccine “container.”

To ensure that only yeast cells successfully producing the antigen are selected, we apply a genetic selection method that Lithuanian researchers have used since 1992. Yeast cells are briefly exposed to formaldehyde; only those carrying a protective genetic instruction survive. Importantly, formaldehyde is not present in the final product. After selection, the yeast is grown and prepared without it, and residual concentrations remain below levels permitted in drinking water. Compared to antibiotic-based selection systems, this method offers advantages.

In mouse studies, we observed that both fresh yeast biomass and dried yeast “crisps” induced an immune response when administered orally. Notably, the mice willingly consumed this preparation. For humans, delivery could involve capsules, but in principle, yeast could also be integrated into fermented beverages such as kvass or beer.

This unconventional idea was explored by U.S. virologist Chris Buck, who attempted to incorporate vaccine-antigen-producing yeast into beer brewing. After analysing his own blood samples before and after consumption, he observed an increase in specific antibody levels. While this self-experiment does not meet the criteria of a clinical trial and must be considered anecdotal, it suggests that the concept may function beyond laboratory models.

To continue his work independently, Buck founded the nonprofit Gusteau Research Corporation and, together with our team, published results and brewing guidelines on the open research platform Zenodo. Although preliminary, these findings provide proof of principle that edible yeast-based vaccines warrant further investigation.

Why have food-based vaccines been considered impossible?

The primary challenge of oral vaccination lies in human biology. During digestion, proteins — including vaccine antigens — are broken down in the stomach. Moreover, immune cells capable of recognising vaccine antigens are located primarily in the intestines, not the stomach. Therefore, an effective oral vaccine must survive gastric acid and reach intestinal immune tissue intact.

Historically, successful oral vaccines have been limited mainly to live, attenuated vaccines targeting intestinal pathogens — such as rotavirus vaccines for infants. These vaccines contain weakened but whole viruses, which strongly stimulate the immune system and are naturally adapted to the gut environment.

In contrast, component or inactivated vaccines — composed of isolated pathogen fragments — often fail to generate sufficiently strong immune responses when taken orally. Even if protected by encapsulation, they frequently induce only local intestinal immunity rather than systemic antibody responses detectable in the bloodstream. This occurs partly because the gut maintains immune tolerance mechanisms that prevent overreaction to food proteins and the microbiota.

In yeast-based vaccines, we believe the yeast cell itself plays a dual role. It protects the antigen from stomach acid and simultaneously acts as a natural adjuvant — an immune-stimulating agent that activates intestinal immune cells. The precise mechanisms remain under investigation.

Our antigen model is the major capsid protein of polyomaviruses. In yeast cells, this protein forms virus-like particles — structures that mimic the shape of a virus and consist of hundreds of protein copies. Purified versions of these particles are already known to be highly immunogenic when administered by injection. Interestingly, in our edible vaccine model, the intact yeast cell is crucial: when disrupted yeast cells containing the same antigen were fed to mice, no immune response developed.

Scientific curiosity meets caution

Naturally, the concept of a “beer vaccine” invites scepticism. No comparable studies have been conducted to date, and regulatory considerations are substantial — especially within the European Union, where genetically modified microorganisms in food are strictly regulated.

However, examples from the United States show that fermented beverages produced with genetically modified yeasts can be legally consumed. Technological feasibility therefore exists, even if regulatory pathways remain complex. Considerable independent research, safety evaluation, and clinical trials would be required before such vaccines could become widely available.

Looking ahead

For me, a Fulbright fellowship and collaboration with U.S. scientists marked the beginning of sustained polyomavirus research in Lithuania. I continue this work with colleagues at the Vilnius University Life Sciences Center, supported by a project funded by the Research Council of Lithuania titled Studies of Polyomavirus Pathogenicity and Host Specificity Factors.

Our goal is not to replace injectable vaccines entirely, but to explore whether alternative formats could complement existing strategies — particularly in regions where cold-chain logistics, costs, or vaccine hesitancy limit coverage.

If we are to improve global immunisation equity, we must be willing to rethink long-standing assumptions. Perhaps, in the future, protection against certain diseases could begin not with a syringe, but with something as simple as a sip.

Emilija Vasiliūnaitė is a  Master of Genetics and PhD Student at Vilnius University.