Abstract
Durable protection against complex pathogens is likely to require immunity that comprises both humoral and cellular responses. While heterologous prime-boost regimens based on recombinant, replication-incompetent Adenoviral vectors (AdV) and adjuvanted protein have been able to induce high levels of concomitant humoral and cellular responses, complex manufacturing and handling in the field may limit their success. To combine the benefits of genetic and protein-based vaccination within one vaccine construct and to facilitate their use, we generated Human Adenovirus 35 (HAdV35) vectors genetically encoding a model antigen based on the Plasmodium falciparum (P. falciparum) circumsporozoite (CS) protein and displaying a truncated version of the same antigen (CSshort) via protein IX on the capsid, with or without a flexible glycine-linker and/or a 45Å-spacer. The four tested pIX-antigen display variants were efficiently incorporated and presented on the HAdV35 capsid irrespective of whether a transgene was encoded or not. Transgene-expression and producibility of the display-/expression vectors were not impeded by the pIX-display. In mice, the pIX-modified vectors induced strong humoral antigen-specific immunity that increased with the inclusion of the linker-/spacer molecules, exceeded the responses induced by the genetic, transgene-expressing HAdV35 vector, and surpassed recombinant protein in potency. In addition, the pIX- display/expression vectors elicited high antigen-specific cellular immune responses that matched those of the genetic HAdV35 vector expressing CS. pIX-modified display-/expression HAdV vectors may therefore be a valuable technology for the development of vaccines against complex pathogens, especially in resource-limited settings.
Highlights
There is growing interest in recombinant, replication-incompetent Adenoviral (AdV) vectors for genetic vaccination due to their ability to induce strong cellular immune responses against the encoded transgenes [1,2,3]
To evaluate protein IX (pIX)-display technology as a vaccine platform, we generated a panel of recombinant, replication-incompetent Human Adenovirus 35 (HAdV35) vectors, displaying a model antigen consisting of a truncated version of the P. falciparum CS protein (CSshort) on pIX
We describe the development and immunological evaluation of replication-incompetent HAdV35 vectors displaying a truncated version of the P. falciparum CS (CSshort) as a model antigen via the small capsid protein IX
Summary
There is growing interest in recombinant, replication-incompetent Adenoviral (AdV) vectors for genetic vaccination due to their ability to induce strong cellular immune responses against the encoded transgenes [1,2,3]. While vectors based on human Adenovirus 5 (HAdV5) are most frequently used, their immunogenicity is impaired by high levels of pre-existing. HAdV35 pIX-display platform and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ’author contributions’ section
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