Prevalence of serum neutralizing antibodies against chimpanzee adenovirus 63 and human adenovirus 5 in Kenyan children, in the context of vaccine vector efficacy

Vaccine. 2009 Jun 2;27(27):3501-4. doi: 10.1016/j.vaccine.2009.03.080. Epub 2009 Apr 16.

Abstract

Vaccination against Plasmodium falciparum malaria could reduce the worldwide burden of this disease, and decrease its high mortality in children. Replication-defective recombinant adenovirus vectors carrying P. falciparum epitopes may be useful as part of a vaccine that raises cellular immunity to the pre-erythrocytic stage of malaria infection. However, existing immunity to the adenovirus vector results in antibody-mediated neutralization of the vaccine vector, and reduced vaccine immunogenicity. Our aim was to examine a population of children who are at risk from P. falciparum malaria for neutralizing immunity to replication-deficient recombinant chimpanzee adenovirus 63 vector (AdC63), compared to human adenovirus 5 vector (AdHu5). We measured 50% and 90% vector neutralization titers in 200 individual sera, taken from a cohort of children from Kenya, using a secreted alkaline phosphatase neutralization assay. We found that 23% of the children (aged 1-6 years) had high-titer neutralizing antibodies to AdHu5, and 4% had high-titer neutralizing antibodies to AdC63. Immunity to both vectors was age-dependent. Low-level neutralization of AdC63 was significantly less frequent than AdHu5 neutralization at the 90% neutralization level. We conclude that AdC63 may be a useful vector as part of a prime-boost malaria vaccine in children.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviruses, Human / immunology*
  • Adenoviruses, Simian / immunology*
  • Animals
  • Antibodies, Viral / blood*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Genetic Vectors / immunology*
  • Humans
  • Infant
  • Malaria Vaccines / immunology*
  • Neutralization Tests
  • Pan troglodytes / virology*
  • Seroepidemiologic Studies
  • Vaccination
  • Vaccines, Synthetic / immunology*

Substances

  • Antibodies, Viral
  • Malaria Vaccines
  • Vaccines, Synthetic