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Influenza A(H5N1) Virus Subunit Vaccine Administered with CaPNP Adjuvant Induce High Virus Neutralization Antibody Titers in Mice

tetano

Editor, Senior Moderator
AAPS PharmSciTech. 2019 Oct 7;20(8):315. doi: 10.1208/s12249-019-1530-9. [h=1]Influenza A(H5N1) Virus Subunit Vaccine Administered with CaPNP Adjuvant Induce High Virus Neutralization Antibody Titers in Mice.[/h]
Morcol T[SUP]1[/SUP], Nagappan P[SUP]2[/SUP], Bell SJD[SUP]3[/SUP], Cawthon AG[SUP]4[/SUP].
[h=3]Author information[/h] 1 CaPtivate Pharmaceuticals LLC, 3805 Old Easton Road, Doylestown, Pennsylvania, 18902, USA. tmorcol@captivatepharma.com. 2 Clark Atlanta University, Atlanta, Georgia, USA. 3 Proventus Bio Inc., Atlanta, Georgia, USA. 4 Battelle, West Jefferson, Ohio, USA.

[h=3]Abstract[/h] The highly pathogenic avian influenza H5N1 virus continues to spread globally in domestic poultry with sporadic transmission to humans. The possibility for its rapid transmission to humans raised global fears for the virus to gain capacity for human-to-human transmission to start a future pandemic. Through direct contact with infected poultry, it caused the largest number of reported cases of severe disease and death in humans of any avian influenza strains. For pandemic preparedness, use of safe and effective vaccine adjuvants and delivery systems to improve vaccine efficacy are considered imperative. We previously demonstrated CaPtivate's proprietary CaP nanoparticles (CaPNP) as a potent vaccine adjuvant/delivery system with ability to induce both humoral and cell-mediated immune responses against many viral or bacterial infections. In this study, we investigated the delivery of insect cell culture-derived recombinant hemagglutinin protein (HA) of A/H5N1/Vietnam/1203/2004 virus using CaPNP. We evaluated the vaccine immunogenicity in mice following two intramuscular doses of 3 μg antigen combined with escalating doses of CaPNP. Our data showed CaPNP-adjuvanted HA(H5N1) vaccines eliciting significantly higher IgG, hemagglutination inhibition, and virus neutralization titers compared to non-adjuvanted vaccine. Among the four adjuvant doses that were tested, CaPNP at 0.24% final concentration elicited the highest IgG and neutralizing antibody titers. We also evaluated the inflammatory response to CaPNP following a single intramuscular injection in guinea pigs and showed that CaPNP does not induce any systemic reaction or adverse effects. Current data further support our earlier studies demonstrating CaPNP as a safe and an effective adjuvant for influenza vaccines.


[h=4]KEYWORDS:[/h] A/H5N1; CaP nanoparticles; adjuvant; pandemic influenza

PMID: 31591662 DOI: 10.1208/s12249-019-1530-9
 
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