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<jats:p>Decades of success with live adenovirus vaccines suggest that replication-competent recombinant adenoviruses (rAds) could serve as effective vectors for immunization against other pathogens. To explore the potential of a live rAd vaccine against malaria, we prepared a viable adenovirus 5 (Ad5) recombinant that displays a B-cell epitope from the circumsporozoite protein (CSP) of<jats:named-content content-type="genus-species">Plasmodium falciparum</jats:named-content>on the virion surface. The recombinant induced<jats:named-content content-type="genus-species">P. falciparum</jats:named-content>sporozoite-neutralizing antibodies in mice. Human adenoviruses do not replicate in mice. Therefore, to examine immunogenicity in a system in which, as in humans, the recombinant replicates, we constructed a similar recombinant in an adenovirus mutant that replicates in monkey cells and immunized four<jats:named-content content-type="genus-species">Aotus nancymaae</jats:named-content>monkeys. The recombinant replicated in the monkeys after intratracheal instillation, the first demonstration of replication of human adenoviruses in New World monkeys. Immunization elicited antibodies both to the<jats:named-content content-type="genus-species">Plasmodium</jats:named-content>epitope and the Ad5 vector. Antibodies from all four monkeys recognized CSP on intact parasites, and plasma from one monkey neutralized sporozoites<jats:italic>in vitro</jats:italic>and conferred partial protection against<jats:named-content content-type="genus-species">P. falciparum</jats:named-content>sporozoite infection after passive transfer to mice. Prior enteric inoculation of two animals with antigenically wild-type adenovirus primed a response to the subsequent intratracheal inoculation, suggesting a route to optimizing performance. A vaccine is not yet available against<jats:named-content content-type="genus-species">P. falciparum</jats:named-content>, which induces the deadliest form of malaria and kills approximately one million children each year. The live capsid display recombinant described here may constitute an early step in a critically needed novel approach to malaria immunization.</jats:p>

Original publication

DOI

10.1128/iai.02626-14

Type

Journal article

Journal

Infection and Immunity

Publisher

American Society for Microbiology

Publication Date

01/2015

Volume

83

Pages

268 - 275