Chimpanzee-origin adenovirus vectors as vaccine carriers

Abstract

Vaccines based on replication-defective adenoviral vectors are being developed for infectious agents and tumorassociated antigens. Early work focused on vaccines derived from a common human serotype of adenovirus, that is, adenovirus of the serotype 5 (AdHu5). Neutralizing antibodies against AdHu5 virus, present in a large percentage of the human population, dampen the efficacy of vaccines based on this carrier. To circumvent this problem, we generated vectors derived from chimpanzee adenoviruses.Here we describe some basic parameters of vectors derived from chimpanzee adenoviruses C68 and C7, including growth characteristics, yields of infectious particles, effects of additional deletions in E3 and E4 and lengths of the inserted foreign sequence as they relate to the suitability for their eventual development as vaccine carriers for clinical use.

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

“…Adenoviral vectors of human and, more recently, chimpanzee serotypes have been described as attractive vaccine vectors as they induce both innate and adaptive responses [30,31], and here we demonstrate that they can also induce responses in the lymphoid tissues of the intestinal mucosa. This implies that imprinting by mucosal dendritic cells is not an absolute requirement for primed T cells to migrate to the gut [32,33].…”

Activated CD4 + CCR5 + T cells in the rectum predict increased SIV acquisition in SIVGag/Tat-vaccinated rhesus macaques

“…As such, the study was designed to determine the effect of the vaccine-induced cellular immune responses on SIV acquisition (and SIV viremia in the event of infection) in the absence of vaccine-induced Env-specific antibodies. The rationale for this approach resides in the strong cellular immunogenicity of the vectors used (14,27) and the demonstrations that cellular immune responses can prevent/abort SIV mac infection in the setting of a CMV-based vector platform (28). In this context, it is possible that the significant correlation between risk of infection and activated CD4 + T cells in the rectal mucosa may not be present if the animals are vaccinated with Env-containing immunogens.…”

Structure-Based Identification of a Major Neutralizing Site in an Adenovirus Hexon

“…One nonhuman serotype that has been proposed as an alternative vector for vaccination is the chimpanzee adenovirus 68 (AdC68) (42). AdC68 is not neutralized by most human adult sera and elicits a strong transgene productspecific immune response in animals already immune to Ad5 (7,33,42). However, because one immunization with an AdC68 vector will induce serotype-specific immunity, multipledose immunization regimens may require the availability of additional vectors.…”

“…Most adenovirus vectors in use have been derived from the human serotype 5 (Ad5). As almost all human adults have been exposed to Ad5, they possess neutralizing antibodies to Ad5 that limit the efficiency of the virus as a delivery vector (7,33,42). Approaches to circumvent the problem of preexisting immunity include chemical modification of Ad5 surface proteins to mask the neutralizing epitopes (4,19,29) and replacement of the immunogenic capsid proteins with those of other serotypes (21,23,32,41,44).…”