Preclinical and Clinical Demonstration of Immunogenicity by mRNA Vaccines against H10N8 and H7N9 Influenza Viruses

TLDR

WHO reports 120 H7N9 cases with 37 deaths in China, underscoring pandemic risk and the need for rapid, safe vaccines, and mRNA platforms’ speed and scalability make them ideal for this purpose. LNP‑formulated, modified mRNA encoding H10N8 or H7N9 hemagglutinin induced rapid, robust immune responses in mice, ferrets, and nonhuman primates, as measured by hemagglutination inhibition and microneutralization assays. A single H7N9 mRNA dose protected mice from lethal challenge, lowered ferret lung viral titers, and phase‑1 H10N8 trials in humans showed high seroconversion with mild adverse events, confirming protective immunogenicity and acceptable tolerability.

Abstract

Recently, the World Health Organization confirmed 120 new human cases of avian H7N9 influenza in China resulting in 37 deaths, highlighting the concern for a potential pandemic and the need for an effective, safe, and high-speed vaccine production platform. Production speed and scale of mRNA-based vaccines make them ideally suited to impede potential pandemic threats. Here we show that lipid nanoparticle (LNP)-formulated, modified mRNA vaccines, encoding hemagglutinin (HA) proteins of H10N8 (A/Jiangxi-Donghu/346/2013) or H7N9 (A/Anhui/1/2013), generated rapid and robust immune responses in mice, ferrets, and nonhuman primates, as measured by hemagglutination inhibition (HAI) and microneutralization (MN) assays. A single dose of H7N9 mRNA protected mice from a lethal challenge and reduced lung viral titers in ferrets. Interim results from a first-in-human, escalating-dose, phase 1 H10N8 study show very high seroconversion rates, demonstrating robust prophylactic immunity in humans. Adverse events (AEs) were mild or moderate with only a few severe and no serious events. These data show that LNP-formulated, modified mRNA vaccines can induce protective immunogenicity with acceptable tolerability profiles.