The chimeric protein domain III-capsid of dengue virus serotype 2 (DEN-2) successfully boosts neutralizing antibodies generated in monkeys upon infection with DEN-2

Clin Vaccine Immunol. 2011 Mar;18(3):455-9. doi: 10.1128/CVI.00382-10. Epub 2011 Jan 5.

Abstract

Use of a heterologous prime-boost strategy based on a combination of nonreplicative immunogens and candidate attenuated virus vaccines against dengue virus in the same schedule is an attractive approach. These combinations may result in a condensed immunization regime for humans, thus reducing the number of doses with attenuated virus and the time spacing. The present work deals with the evaluation of the heterologous prime-boost strategy combining a novel chimeric protein (domain III-capsid) of dengue virus serotype 2 (DEN-2) and the infective homologous virus in the same immunization schedule in monkeys. Primed monkeys received one dose of infective DEN-2 and were then vaccinated with the recombinant protein. We found that animals developed a neutralizing antibody response after the infective dose and were notably boosted with a second dose of the chimeric protein 3 months later. The neutralizing antibodies induced were long lasting, and animals also showed the ability to induce a specific cellular response 6 months after the booster dose. As a conclusion, we can state that the domain III region, when it is properly presented as a fusion protein to the immune system, is able to recall the neutralizing antibody response elicited following homologous virus infection in monkeys. Further prime-boost approaches can be performed in a condensed regime combining the chimeric domain III-capsid protein and candidate live attenuated vaccines against DEN-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood*
  • Antibodies, Viral / blood*
  • Capsid / immunology*
  • Chlorocebus aethiops
  • Dengue Vaccines / genetics
  • Dengue Vaccines / immunology*
  • Dengue Virus / immunology*
  • Immunization, Secondary / methods*
  • Time Factors
  • Vaccination / methods*
  • Vaccines, Attenuated / genetics
  • Vaccines, Attenuated / immunology
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Dengue Vaccines
  • Vaccines, Attenuated
  • Vaccines, Synthetic