Oral norovirus vaccine passes safety testing with strong immune response in older adults

 Researchers at Vaxart Inc. and the Center for Vaccine Development at the University of Maryland School of Medicine evaluated the safety and immunogenicity of an oral norovirus vaccine tablet, VXA-G1.1-NN. Results indicate that the vaccine was safe and well tolerated while eliciting robust systemic and mucosal immune responses in adults aged 55 to 80 years.

Norovirus infections cause approximately 20 million cases of acute gastroenteritis annually in the United States, leading to 70,000 hospitalizations and up to 800 deaths. The economic impact is estimated at $10.6 billion per year.

Older adults, particularly those in long-term care facilities, are disproportionately affected, with 90% of norovirus-associated deaths occurring in individuals aged 65 and older. No licensed vaccine currently exists to prevent norovirus infections, despite the significant health care burden it imposes.

In the study, "An Oral Norovirus Vaccine Tablet Was Safe and Elicited Mucosal Immunity in Older Adults in a Phase 1b Clinical Trial," published in Science Translational Medicine, researchers conducted a randomized, double-blind, placebo-controlled trial to assess the safety and immunogenicity of VXA-G1.1-NN in healthy older adults.

A total of 65 participants aged 55 to 80 years were enrolled at three clinical sites in the United States. Participants were randomized to receive either the oral VXA-G1.1-NN vaccine or a placebo at a 2:1 ratio. The vaccine was administered at three dose levels (low, medium, and high) using a prime-boost strategy, with doses given 28 days apart.

Primary outcomes included safety and tolerability, measured by adverse events. Secondary outcomes assessed immunogenicity, including serum antibody responses, functional antibody activity, mucosal immunity, and cellular immune responses.

Vaccination with VXA-G1.1-NN was well tolerated across all dose levels. No serious adverse events or vaccine-related Grade 3 reactions were reported. Mild to moderate symptoms, including headache and malaise, were the most common side effects. Solicited adverse events were reported at lower rates in the high-dose group compared to lower doses.

Vaccination induced dose-dependent increases in VP1-specific serum immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies. Serum IgA and IgG responses remained elevated above baseline for 210 days. Functional antibodies, measured through a Norovirus Blocking Antibody Assay (NBAA), showed significant increases in the high-dose group, indicating neutralizing potential against the virus.

Robust mucosal immune responses were observed. Salivary and nasal IgA concentrations increased significantly by day 28 and remained elevated through day 210. Antibody-secreting cells expressing the gut-homing marker α4β7 were detected one week post-vaccination, supporting the vaccine's ability to induce a strong mucosal response.

Similar immune responses were observed between the current older adult participants (55 to 80 years) and younger adults (aged 18 to 49 years) from a prior clinical trial. A cross-study analysis showed comparable serum antibody titers, mucosal IgA levels, and antigen-specific B cell responses between the two age groups, suggesting that the vaccine's effectiveness was not significantly impacted by immunosenescence.

Oral administration of VXA-G1.1-NN was found to be safe, well tolerated, and capable of generating durable immune responses in older adults. The study supports the feasibility of an oral vaccine for norovirus, which could offer advantages over injectable vaccines, including ease of distribution and self-administration.

As a phase 1 safety trial, further trials are required to evaluate effectiveness of the vaccine. A phase 2 clinical trial is currently investigating a bivalent version targeting both GI.1 and GII.4 norovirus genogroups to explore potential cross-protection against diverse norovirus strains.

More information: Becca A. Flitter et al, An oral norovirus vaccine tablet was safe and elicited mucosal immunity in older adults in a phase 1b clinical trial, Science Translational Medicine (2025). DOI: 10.1126/scitranslmed.ads0556

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