A Replication-Defective Human Adenovirus Recombinant Serves as a Highly Efficacious Vaccine Carrier

Abstract

In this manuscript, an E1 and E3 deleted adenoviral recombinant expressing the rabies virus glycoprotein (G protein) under the control of the cytomegalovirus early promoter was tested for induction of a rabies virus-specific immune response in mice. The construct was found to induce neutralizing antibodies and cytolytic T cells to rabies virus. Mice vaccinated with the adenoviral construct either by the systemic route or by application into the airways were protected against a subsequent infection with a virulent strain of rabies virus. The efficacy of the replication-defective construct was far superior to that of a well-characterized vaccinia rabies glycoprotein recombinant.

Chimpanzee-origin adenovirus vectors as vaccine carriers

“…Adenoviral vectors were generated from molecular clones, propagated, purified and quality controlled (PFU-to-vp ratios, RCA content, genome integrity) as described elsewhere. 11,15 Inserts: clade B SIVgag, SIVgag-pol, SIVgag-pol-nef, SIVpol, SIVnef, HIVgp140 and HIVgag were generous gifts from G Nabel at the NIH/VRC, Bethesda, MD, USA. HIVgag37 was a generous gift from G Pavlakis at the NIH/NCI, Fredrick, MD.…”

“…Most of the past efforts focused on human Ads, such as those of the common serotype 5 (AdHu5), which cause mild upper respiratory symptoms upon natural infections. Both replication competent 9,10 and E1-deleted (DE1) replication-defective AdHu5 vectors have been developed as vaccine carriers and have shown efficacy in mice, 11 dogs 12,13 and nonhuman primates (NHPs). 7 E1-deleted AdHu5 vectors also performed well in clinical trials.…”

Intramuscular rather than oral administration of replication-defective adenoviral vaccine vector induces specific CD8+ T cell responses in the gut

“…Some evidence suggests that the route of immunization influences the trafficking of T cells [3,4], and some routes including mucosal administration of viral vectors have been shown to be efficient at inducing mucosal immune responses which may sometimes be protective [3,[5][6][7][8]. Mucosal T cells receive instructions to migrate to the intestines during priming by dendritic cells in the mesenteric lymph nodes (MLN) and other inductive sites [9,10].…”

Recombinant Viral Vector Vaccines for the Veterinary Use.

“…Such replication-incompetent adenovirus vectors are currently being studied as attractive candidates mainly for gene therapy purposes. Immunization of experimental animals with the recombinant adenovirus containing genes in the E1 region can induce a systemic immune response to the foreign gene product even in the absence of viral replication and provide a protection against subsequent challenge [1,22,28,71,92,128]. Despite the safety advantages of replication incompetent viruses, the drawback of using such mutants is that high titers of virus must be injected into animals to elicit a strong immune response.…”