Immunogenicity and protection efficacy of subunit-based smallpox vaccines using variola major antigens

Virology. 2008 Feb 5;371(1):98-107. doi: 10.1016/j.virol.2007.09.029. Epub 2007 Oct 24.

Abstract

The viral strain responsible for smallpox infection is variola major (VARV). As a result of the successful eradication of smallpox with the vaccinia virus (VACV), the general population is no longer required to receive a smallpox vaccine, and will have no protection against smallpox. This lack of immunity is a concern due to the potential for use of smallpox as a biological weapon. Considerable progress has been made in the development of subunit-based smallpox vaccines resulting from the identification of VACV protective antigens. It also offers the possibility of using antigens from VARV to formulate the next generation subunit-based smallpox vaccines. Here, we show that codon-optimized DNA vaccines expressing three VARV antigens (A30, B7 and F8) and their recombinant protein counterparts elicited high-titer, cross-reactive, VACV neutralizing antibody responses in mice. Vaccinated mice were protected from intraperitoneal and intranasal challenges with VACV. These results suggest the feasibility of a subunit smallpox vaccine based on VARV antigen sequences to induce immunity against poxvirus infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology
  • Body Weight
  • Cell Line
  • Chemoprevention / methods
  • Enzyme-Linked Immunosorbent Assay
  • Escherichia coli / genetics
  • Feasibility Studies
  • Female
  • Humans
  • Immunization Schedule
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology
  • Kidney / cytology
  • Mice
  • Mice, Inbred BALB C
  • Models, Animal
  • Molecular Sequence Data
  • Neutralization Tests
  • Sequence Homology, Amino Acid
  • Smallpox / immunology
  • Smallpox / prevention & control*
  • Smallpox Vaccine / administration & dosage
  • Smallpox Vaccine / genetics
  • Smallpox Vaccine / immunology*
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology*
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • Vaccines, Subunit / immunology
  • Vaccinia virus / immunology*
  • Variola virus / genetics
  • Variola virus / immunology
  • Variola virus / pathogenicity
  • Viral Vaccines*

Substances

  • Antigens, Viral
  • Immunoglobulin G
  • Smallpox Vaccine
  • Vaccines, Attenuated
  • Vaccines, DNA
  • Vaccines, Subunit
  • Viral Vaccines