Influenza virus infections are a major public health concern and cause significant morbidity and mortality worldwide. Current influenza virus vaccines are an effective countermeasure against infection but need to be reformulated almost every year owing to antigenic drift. Furthermore, these vaccines do not protect against novel pandemic strains, and the timely production of pandemic vaccines remains problematic because of the limitations of current technology. Several improvements have been made recently to enhance immune protection induced by seasonal and pandemic vaccines, and to speed up production in case of a pandemic. Importantly, vaccine constructs that induce broad or even universal influenza virus protection are currently in preclinical and clinical development.

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Advances in the development of influenza virus vaccines.

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

mRNA vaccines have the potential to tackle many unmet medical needs that are unable to be addressed with conventional vaccine technologies. A potent and well-tolerated delivery technology is integral to fully realizing the potential of mRNA vaccines. Pre-clinical and clinical studies have demonstrated that mRNA delivered intramuscularly (IM) with first-generation lipid nanoparticles (LNPs) generates robust immune responses. Despite progress made over the past several years, there remains significant opportunity for improvement, as the most advanced LNPs were designed for intravenous (IV) delivery of siRNA to the liver. Here, we screened a panel of proprietary biodegradable ionizable lipids for both expression and immunogenicity in a rodent model when administered IM. A subset of compounds was selected and further evaluated for tolerability, immunogenicity, and expression in rodents and non-human primates (NHPs). A lead formulation was identified that yielded a robust immune response with improved tolerability. More importantly for vaccines, increased innate immune stimulation driven by LNPs does not equate to increased immunogenicity, illustrating that mRNA vaccine tolerability can be improved without affecting potency.

Optimization of Lipid Nanoparticles for Intramuscular Administration of mRNA Vaccines

Genesis, Evolution and Prevalence of H5N6 Avian Influenza Viruses in China

Both Neutralizing and Non-Neutralizing Human H7N9 Influenza Vaccine-Induced Monoclonal Antibodies Confer Protection.

http://pic.biodiscover.com/files/9/uy/biodiscover1417427541.9040846.pdf

Jiyi Fan

Papers

Clinical and epidemiological characteristics of a fatal case of avian influenza A H10N8 virus infection: a descriptive study