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A nanoemulsion-adjuvanted intranasal H5N1 influenza vaccine protects ferrets against homologous and heterologous H5N1 lethal challenge. 2019

Douglas Smith, and Stephen J Streatfield, and Hugo Acosta, and Shyamala Ganesan, and Ali Fattom
BlueWillow Biologics, Ann Arbor, MI, United States.

Flu vaccines administered intramuscularly (IM) have shown seasonally fluctuating efficacy, 20-60%, throughout the last 15 years. We formulated a recombinant H5 (rH5) in our Nanovax® (NE01) (rH5/NE01) adjuvant for intranasal vaccination in ferrets. We evaluated the regimen, one vs two immunization, and cross clade protection a ferret challenge model. Plant derived recombinant H5 (rH5) antigen was formulated with NE01 and administered intranasally to ferrets. Immunogenicity (IgG), hemagglutination inhibition (HI), and protection against lethal challenge, were measured following one or two immunizations. Protection against homologous (strain A/Indo) and heterologous (strain A/Vn) was evaluated in ferrets following two immunizations. IN immunization with rH5/NE01 induced significant IgG levels after one and two immunizations. One vaccination did not induce any HI while low HI was measured after two immunizations. Homologous challenge with H5N1 A/ Indonesia showed 100% survival, with minimal weight loss in animals vaccinated twice compared to the unvaccinated controls. Analysis of nasal wash from these challenged ferrets vaccinated twice showed decreased viral shedding compared to unvaccinated controls. Interestingly, animals that received one vaccination showed 88% survival with moderate weight loss. Cross clade protection was evaluated using an increased antigen dose (45 µg rH5). Vaccinated animals demonstrated increased IgG and HAI antibody responses. Both homologous (A/Indo) and heterologous challenge (A/Vietnam) following two immunizations showed 100% survival with no loss of body weight. However viral clearance was more rapid against the homologous (day 3) compared to the heterologous (day 5) post challenge. Intranasal administration of NE01 adjuvant-formulated rH5 vaccine elicited systemic and probably mucosal immunity that conferred protection against lethal challenge with homologous or heterologous viral strains. It also enhanced viral clearance with decreased shedding. These outcomes strongly suggest that intranasal immunization using NE01 against flu infections warrants clinical testing.

UI MeSH Term Description Entries
D007074 Immunoglobulin G The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B. Gamma Globulin, 7S,IgG,IgG Antibody,Allerglobuline,IgG(T),IgG1,IgG2,IgG2A,IgG2B,IgG3,IgG4,Immunoglobulin GT,Polyglobin,7S Gamma Globulin,Antibody, IgG,GT, Immunoglobulin
D007117 Immunization, Secondary Any immunization following a primary immunization and involving exposure to the same or a closely related antigen. Immunization, Booster,Revaccination,Secondary Immunization,Booster Immunization,Booster Immunizations,Immunizations, Booster,Immunizations, Secondary,Revaccinations,Secondary Immunizations
D007252 Influenza Vaccines Vaccines used to prevent infection by viruses in the family ORTHOMYXOVIRIDAE. It includes both killed and attenuated vaccines. The composition of the vaccines is changed each year in response to antigenic shifts and changes in prevalence of influenza virus strains. The flu vaccines may be mono- or multi-valent, which contains one or more ALPHAINFLUENZAVIRUS and BETAINFLUENZAVIRUS strains. Flu Vaccine,Influenzavirus Vaccine,Monovalent Influenza Vaccine,Universal Flu Vaccine,Universal Influenza Vaccine,Flu Vaccines,High-Dose Trivalent Influenza Vaccine,Influenza Vaccine,Influenza Virus Vaccine,Influenza Virus Vaccines,Influenzavirus Vaccines,Intranasal Live-Attenuated Influenza Vaccine,LAIV Vaccine,Monovalent Influenza Vaccines,Quadrivalent Influenza Vaccine,Trivalent Influenza Vaccine,Trivalent Live Attenuated Influenza Vaccine,Universal Flu Vaccines,Universal Influenza Vaccines,Flu Vaccine, Universal,High Dose Trivalent Influenza Vaccine,Influenza Vaccine, Monovalent,Influenza Vaccine, Quadrivalent,Influenza Vaccine, Trivalent,Influenza Vaccine, Universal,Intranasal Live Attenuated Influenza Vaccine,Vaccine, Flu,Vaccine, Influenza,Vaccine, Influenza Virus,Vaccine, Influenzavirus,Vaccine, LAIV,Vaccine, Monovalent Influenza,Vaccine, Quadrivalent Influenza,Vaccine, Trivalent Influenza,Virus Vaccine, Influenza
D009976 Orthomyxoviridae Infections Virus diseases caused by the ORTHOMYXOVIRIDAE. Orthomyxovirus Infections,Infections, Orthomyxoviridae,Infections, Orthomyxovirus,Swine Influenza,Infection, Orthomyxoviridae,Infection, Orthomyxovirus,Influenza, Swine,Orthomyxoviridae Infection,Orthomyxovirus Infection
D011994 Recombinant Proteins Proteins prepared by recombinant DNA technology. Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D005289 Ferrets Semidomesticated variety of European polecat much used for hunting RODENTS and/or RABBITS and as a laboratory animal. It is in the subfamily Mustelinae, family MUSTELIDAE. Domestic Polecat,Domestic Polecats,European Polecat,European Polecats,Ferret,Mustela putorius,Mustela putorius furo,Polecat, Domestic,Polecat, European,Polecats, Domestic,Polecats, European
D000276 Adjuvants, Immunologic Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Immunoactivators,Immunoadjuvant,Immunoadjuvants,Immunologic Adjuvant,Immunopotentiator,Immunopotentiators,Immunostimulant,Immunostimulants,Adjuvant, Immunologic,Adjuvants, Immunological,Immunologic Adjuvants,Immunological Adjuvant,Adjuvant, Immunological,Immunological Adjuvants
D000281 Administration, Intranasal Delivery of medications through the nasal mucosa. Drug Administration, Intranasal,Administration, Intranasal Drug,Administration, Nasal,Intranasal Administration,Intranasal Drug Administration,Administrations, Intranasal,Administrations, Intranasal Drug,Administrations, Nasal,Drug Administrations, Intranasal,Intranasal Administrations,Intranasal Drug Administrations,Nasal Administration,Nasal Administrations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000914 Antibodies, Viral Immunoglobulins produced in response to VIRAL ANTIGENS. Viral Antibodies

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