A single injection of mRNA-1403, a multivalent norovirus mRNA vaccine, induces a robust serum histo-blood group antigen (HBGA)-blocking antibody response across all dose levels in adults, as shown by interim results of an ongoing phase I/II trial presented at IDWeek 2024. Comparable findings have been observed with serum virus-like particle (VLP)-binding antibody responses.

“Available data from this ongoing phase I/II study show that mRNA-1403 was generally safe and well-tolerated and induced antigen-specific immune responses at all dose levels in both younger and older healthy adults,” said presenting author Dr Till Schoofs, director, Clinical Development Infectious Disease, Moderna, Inc., US. “These results informed dose selection for a phase III efficacy study in adults.”

Schoofs and his team are currently assessing the safety and immunogenicity of mRNA-1403 in healthy adults aged 18?80 years in this phase I/II randomized, placebo-controlled study.

In phase I, healthy younger (18?49 years) and older (60?80 years) adults were randomly allocated to receive one of four dose levels of mRNA-1403 given as two doses, one dose level of mRNA-1403 given as a single dose, or placebo. In phase II, a larger sample size of healthy adults aged 18?80 years received three dose levels of the vaccine given as a single-dose schedule.

Safety

The first phase of the study included 335 adults who received one or two doses of mRNA-1403 or placebo. The vaccine was well-tolerated in all dose levels, showing now serious safety concerns through 8 months of follow-up from the first dose. [IDWeek 2024, abstract 575]

At 1 month, individuals who received a single injection of mRNA-1403 demonstrated robust levels of HBGA-blocking antibodies and binding antibodies against vaccine-matched norovirus genotypes across all dose levels examined.

No deaths or adverse events (AE) leading to study withdrawal were reported. One participant discontinued the study due to an AE, but it was deemed unrelated to the vaccine.

In phase II, 616 healthy adults received a single injection of one of three selected dose levels of mRNA-1403 or placebo. In this larger sample size, results at 1-month follow-up confirmed the safety and immunogenicity of a single-dose schedule of all three dose levels of mRNA-1403.

“No safety concerns [were] identified for mRNA-1403 through 8 months of follow-up in phase I and 1 month of follow-up in phase II,” and “no clinically meaningful or dose-dependent trends in unsolicited AEs evident among participants” were observed, according to Schoofs.

“Available data supported [the] initiation of a phase III study evaluating efficacy of a single-dose primary schedule of mRNA-1403 in [the] prevention of moderate-to-severe norovirus acute gastroenteritis (AGE) in adults,” he added.

Norovirus is the leading cause of AGE, with approximately 685 million cases and 200,000 deaths annually across the globe. [https://www.cdc.gov/norovirus/downloads/global-burden-report.pdf]

“Currently, there is no licensed norovirus vaccine,” Schoofs said. “Norovirus’ high genetic diversity coupled with genotype-specific immune responses indicate that a multivalent approach may be required to generate a broadly protective vaccine.”