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

: Smith, D.; Streatfield, S.J.; Acosta, H.; Ganesan, S.; Fattom, A.


Vaccine 37 (2019), Nr.42, S.6162-6170
ISSN: 0264-410X
ISSN: 1873-2518
Fraunhofer CMB ()

Background: 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 (R) (NE01) (rH5/NE01) adjuvant for intranasal vaccination in ferrets. We evaluated the regimen, one vs two immunization, and cross Glade protection a ferret challenge model. Methods: 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. Results: 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 Glade protection was evaluated using an increased antigen dose (45 jig 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. Conclusion: 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.