Comparison of T cell immune responses induced by vectored HIV vaccines in non-human primates and humans

Comparison of Vaccine-Induced Effector CD8 T Cell Responses Directed against Self- and Non–Self-Tumor Antigens: Implications for Cancer Immunotherapy

“…Among viruses investigated for vaccine purposes, replication defective adenovirus vectors have shown great potential, because they have been found to induce potent Ab and CD8 T cell responses in mice, primates, and humans (10)(11)(12). Adenoviral vectors are also excellent vaccine candidates for several more technical reasons: they are well characterized, easy to manipulate, stable, and safe to use even in immunodeficient hosts.…”

Harnessing the Potential of Adenovirus Vectored Vaccines

“…This in turn leads to poorer cytokine producing competence. The relative importance of hematopoietic and non-hematopoietic antigen presentation at doses below ~10 9 particles is as yet undetermined, but some studies in mice and primates as well as humans have demonstrated the relative stability of the response within 10-fold variations of the inoculum (Bassett et al, 2011;Bett et al, 2010), and we have seen a plateau of the response between ~10 9 to ~10 8 particles administered s.c., with a gradual reduction of the magnitude of the response upon further dose reductions (Holst PJ, Thomsen AR and Christensen JP,unpublished and (Flatz et al, 2010)). A possible explanation for these plateaus could be that these doses are sufficient to target all the relevant professional antigen presenting cells present at the injection site, and that the major difference between the doses are in the degree of non-dendritic cell targeted transduction.…”

“…As murine studies reporting an exhausted phenotype of adenovirus induced CD8+ T cells have typically involved virus doses in the range of 10 10 -10 11 viral particles (Tatsis et al, 2007a;Yang et al, 2006), one might question the relevance of the results obtained when it comes to human or primate vaccination, where the virus dose is typically in the order of 10 10 -10 11 particles (Bett et al, 2010). In contrast to the studies using high doses of adenoviral vectors in mice, CD8+ T cells induced by adenoviral vaccination in primates and humans are cytokine competent and cytotoxic cells, but seemingly terminally differentiated effectorlike cells are found in the circulation for extended periods of time.…”

“…In this context, the use of recombinant virus vectored vaccines may be a promising future concept that combines important features of live attenuated vaccines with greater safety and the ability to target any imaginable antigen. Among the virus vectors investigated for vaccine purposes, adenovirus vectors have received considerable attention and today stand among the most potent tools available for induction of antibody and CD8+ T cell responses in mice, primates and humans (Barefoot et al, 2008;Bett et al, 2010;Shiver et al, 2002). Adenovirus vectored vaccines has, however, also been implicated in one of the most spectacular HIV vaccine failures (Buchbinder et al, 2008), and some papers describe either undesirable attributes of the adenovirus induced T cell response or properties of vector specific responses, which may increase mucosal HIV transmission (Benlahrech et al, 2009;Perreau et al, 2008).…”

HIV-1 vaccines

“…In contrast, prime-boost vaccine regimens and vaccines using adjuvant formulations did not correlate between rhesus macaques and humans. 99 An emerging understanding of the early events in mucosal SIV, SHIV, and HIV-1 infections has been recently reviewed 100,101 justifying the need to develop vaccines inducing both humoral (either local produced or resulting from transudation of plasma antibodies) and cell-mediated mucosal immune responses. A relatively small number of immune effectors at the mucosal site of entry might be at the right place at the right time to be "enough and soon enough" to clear infection.…”