title: Prevalence of serum neutralizing antibodies against chimpanzee adenovirus 63 and human adenovirus 5 in Kenyan children, in the context of vaccine vector efficacy.
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.
authors.forename: M
authors.initials: M
authors.lastname: Dudareva
authors.forename: L
authors.initials: L
authors.lastname: Andrews
authors.forename: S C
authors.initials: SC
authors.lastname: Gilbert
authors.forename: P
authors.initials: P
authors.lastname: Bejon
authors.forename: K
authors.initials: K
authors.lastname: Marsh
authors.forename: J
authors.initials: J
authors.lastname: Mwacharo
authors.forename: O
authors.initials: O
authors.lastname: Kai
authors.forename: A
authors.initials: A
authors.lastname: Nicosia
authors.forename: A V S
authors.initials: AV
authors.lastname: Hill
mesh_terms: D000260:Adenoviruses, Human / Q000276:immunology*; D000261:Adenoviruses, Simian / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005822:Genetic Vectors / Q000276:immunology*; D006801:Humans; D007223:Infant; D017780:Malaria Vaccines / Q000276:immunology*; D009500:Neutralization Tests; D002679:Pan troglodytes / Q000821:virology*; D016036:Seroepidemiologic Studies; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D017780:Malaria Vaccines; D014614:Vaccines, Synthetic