Non-chromatographic preparation of a bacterially produced single-shot modular virus-like particle capsomere vaccine for avian influenza

Vaccine. 2015 Nov 4;33(44):5960-5. doi: 10.1016/j.vaccine.2015.08.100. Epub 2015 Sep 25.

Abstract

Highly pathogenic avian influenza (HPAI) causes significant economic loss, reduced food security and poses an ongoing pandemic threat. Poultry vaccination significantly decreases these problems and recognizes that the health of humans, animals and ecosystems are connected. Low-cost manufacture of poultry vaccine matched quickly to the ever-changing circulating strain is needed for effective vaccination. Here, we re-engineered the process to manufacture bacterially synthesized modular capsomere comprising influenza M2e, previously shown to confer complete protection in challenged mice, for application in poultry. Modular capsomere was prepared using a simplified non-chromatographic salting-out precipitation method and its immunogenicity tested in vivo in poultry. Modular capsomere crudely purified by precipitation (pCapM2e) contained more contaminants than equivalent product purified by chromatography (cCapM2e). Unadjuvanted pCapM2e containing 80 EU of endotoxin per dose was inferior to highly purified and adjuvanted cCapM2e (2 EU per dose). However, addition of adjuvant to pCapM2e resulting in high immunogenicity after only a single dose of vaccination, yet without any local adverse reaction. This finding suggests a strong synergy between adjuvant, antigen and contaminants, and the possible existence of a "Goldilocks" level of contaminants, where high immunogenicity and low reactogenicity can be obtained in a single-shot vaccination. The simplified process offers potential cost and speed advantages to address the needs in influenza poultry vaccination in low-cost veterinary markets.

Keywords: Capsomere; Influenza; Polyomavirus; Poultry; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antibodies, Viral / blood
  • Chemical Precipitation*
  • Chickens
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Immunoglobulin G / blood
  • Influenza in Birds / immunology
  • Influenza in Birds / prevention & control*
  • Mice
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / genetics
  • Recombinant Proteins / immunology
  • Recombinant Proteins / isolation & purification
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology
  • Vaccines, Synthetic / isolation & purification
  • Vaccines, Virus-Like Particle / administration & dosage
  • Vaccines, Virus-Like Particle / genetics
  • Vaccines, Virus-Like Particle / immunology*
  • Vaccines, Virus-Like Particle / isolation & purification*
  • Viral Matrix Proteins / administration & dosage
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / immunology*
  • Viral Matrix Proteins / isolation & purification*

Substances

  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Immunoglobulin G
  • M2 protein, Influenza A virus
  • Recombinant Proteins
  • Vaccines, Synthetic
  • Vaccines, Virus-Like Particle
  • Viral Matrix Proteins