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AAPS PharmSciTech

, 20:315 | Cite as

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

  • Tulin MorcolEmail author
  • Peri Nagappan
  • Stephen J. D. Bell
  • Andrew G. Cawthon
Research Article

Abstract

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.

KEY WORDS

CaP nanoparticles adjuvant A/H5N1 pandemic influenza 

Notes

Acknowledgments

This study was supported by BioSante Pharmaceuticals Inc. and by CaPtivate Pharmaceuticals LLC. The authors thank BioCon Inc. (Rockville, MD) small animal facility staff for performing the animal studies, Battelle scientists for performing HAI and MN assays, and IITRI facility staff and scientists for performing the acute toxicity studies.

Compliance with Ethical Standards

Ethics Statement

All immunization studies were performed at BioCon Inc. (Rockville, MD) in the company’s Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC)-accredited Laboratory Animal Research Facility. Animals were housed according to Office of Laboratory Animal Welfare (OLAW) and AAALAC Guidelines. All animal experiments and related protocols were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of BioCon. Experiments were conducted in accordance with the guidelines set out by the AAALAC. Acute toxicity studies were performed separately with contract to IIT Research Institute (IITRI-Chicago, IL.) and in accordance with U.S. Food and Drug Administration (FDA) Good Laboratory Practice (GLP) Regulations as set forth in the Code of Federal Regulations.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Tulin Morcol
    • 1
    Email author
  • Peri Nagappan
    • 2
  • Stephen J. D. Bell
    • 3
  • Andrew G. Cawthon
    • 4
  1. 1.CaPtivate Pharmaceuticals LLCDoylestownUSA
  2. 2.Clark Atlanta UniversityAtlantaUSA
  3. 3.Proventus Bio Inc.AtlantaUSA
  4. 4.BattelleWest JeffersonUSA

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