The specter of a severe influenza pandemic remains one of the most credible and consequential threats in global health security. As H5N1 continues to circulate among U.S. dairy cattle and generate sporadic human infections, the urgency of developing effective, rapidly deployable vaccines has never been clearer. New clinical data now offer some cautious optimism: an mRNA-based pandemic influenza vaccine platform is showing a favorable safety profile and robust immune responses against two avian influenza subtypes that public health officials have long flagged as pandemic threats.
The Phase 1/2 findings for mRNA-1018, Moderna’s investigational pandemic influenza vaccine candidates, were published in Clinical Infectious Diseases. The candidates target two influenza A virus groups with established pandemic potential: H5 subtypes (including H5N8 and H5N1) and H7N9 — the same strains responsible for documented waves of severe human illness over the past decade.
Trial Design and Participants
The study was conducted in two parts. Part A enrolled 1,195 healthy adults aged 18 and older across four vaccine candidate arms — H5N8, H5-only, H7N9, and H7-only mRNA-1018 — at varying dose levels of 25, 50, and 100 µg. Part B enrolled an additional 304 participants in a separate arm evaluating H5-only-CG mRNA-1018 at dose levels of 12.5, 25, and 50 µg. In total, 1,506 participants were randomized across both parts. The H5 vaccine sequences were drawn specifically from clade 2.3.4.4b — the same genetic lineage driving the current HPAI outbreak in U.S. dairy cattle and linked to recent human cases. Follow-up extended approximately seven months after vaccination, with blood sampling at days 1, 22, 43, and 205.
A Well-Tolerated Vaccine Across Age Groups and Dose Levels
The most common local reaction was injection-site pain; the most common systemic reactions were fatigue and headache. The vast majority of these reactions were grade 1 or 2 in severity, meaning mild to moderate, transient, and self-resolving, with median duration of two days. Grade 3 events were infrequent, and no grade 4 solicited adverse reactions were recorded in either part. One event of acute thyroiditis was assessed as vaccine-related and resulted in study discontinuation. Younger participants aged 18 to 64 reported adverse reactions more frequently than those 65 and older in Part A, a pattern consistent with findings from other mRNA vaccines.
Immune Responses That Are Strong, Dose-Dependent, and Durable
All five candidates induced measurable functional immune responses — assessed by hemagglutination inhibition (HAI), neuraminidase inhibition, and microneutralization assays — against homologous pandemic virus strains. These responses were detectable before the second dose, peaked within approximately three weeks after the second injection at day 43, and remained above baseline through the day 205 follow-up.
At the 100 µg dose level in Part A, day 43 HAI geometric mean titers were 249.1 for H5N8 and 87.7 for H7N9, with seroconversion rates of 94.4% and 89.4% respectively. H5-only candidates achieved comparable HAI responses, with the 50 µg dose yielding a GMT of 285.8 and a 98.9% seroconversion rate. In Part B, the H5-only-CG candidate at 50 µg achieved a day 43 HAI GMT of 340.9 with 100% seroconversion. Immune response magnitude increased with vaccine dose across all candidates. Notably, including neuraminidase antigens in the H5N8 and H7N9 formulations did not diminish hemagglutinin-directed HAI responses, a finding with potential implications for multivalent formulation development.
By day 205, HAI titers had declined from peak levels but remained substantially above baseline across most arms, particularly for H5-containing candidates. Microneutralization titers showed a similar pattern of durable response, with the H5-only 50 µg arm maintaining a day 205 GMT of 59.2, compared to a baseline of approximately 5.4.
These results compare favorably with existing licensed pandemic influenza vaccines, which have historically required adjuvants to achieve adequate immunogenicity, particularly in older adults.
Why This Matters for Pandemic Preparedness
Between February 2024 and September 2025, 70 confirmed H5N1 human infections were reported in the United States, with no documented human-to-human transmission — a threshold whose crossing would signal a fundamental shift in pandemic risk. The mRNA platform’s defining advantages — rapid sequence-to-dose timelines, scalable manufacturing, and precise antigenic matching — make it uniquely suited for pandemic response, where weeks or months of lead time can determine whether a vaccine arrives before or after a wave of severe disease.
These findings, combined with positive Phase 3 efficacy data for mRNA-1010, Moderna’s seasonal influenza vaccine developed on the same platform, strengthen the scientific and regulatory rationale for advancing mRNA-1018 through pivotal trials.
Sources and further reading:
Cosgrove C, Avanesov A, et al. A Phase 1/2 Dose-Ranging Safety and Immunogenicity Study of mRNA-Based Candidate Pandemic Influenza Vaccines in Healthy Adults. Clinical Infectious Diseases. April 25, 2026.