Novel adenovirus vaccine vectors based on the enteric-tropic serotype 41

Abstract

Replication-defective adenovirus vectors, primarily developed from serotype 5 (Ad5) viruses, have been widely used for gene transfer and vaccination approaches. Vectors based on other serotypes of adenovirus could be used in conjunction with, or in place of, Ad5 vectors. In this study, Ad41, an enteric adenovirus usually described as 'non-cultivable' or 'fastidious,' has been successfully cloned, rescued and propagated on 293-ORF6 cells. The complementation capabilities of this cell line allow generation of Ad41 vectors at titers comparable to those obtained for Ad5 vectors. Mice immunized with an Ad41 vector containing an HIV envelope (Env) gene mounted anti-Env cellular and humoral immune responses. Ad41-Env vectors appear to be particularly attractive when used in heterologous prime-boost regimens, where they induce significantly higher cellular immune responses to HIV-Env than Ad5-based regimens. Ad41-based constructs are attractive vaccine vectors alone or in combination with Ad5 adenovectors, since each vector type can provide circumvention of pre-existing immunity to the other.

Wild-type adenoviruses from groups A–F evoke unique innate immune responses, of which HAd3 and SAd23 are partially complement dependent

“…25 In most cases, alternative serotype Ads are not cross-neutralized by antibodies directed against another serotype. 26,27 Furthermore, the incidence rate of seroconversion to many alternative serotype HAds in many cases are significantly lower than the seroconversion rates noted for HAd5. 28 These facts have justified multiple investigations into the use of alternative serotype Ads for potential use in numerous human gene transfer applications.…”

Changing the adenovirus fiber for retaining gene delivery efficacy in the presence of neutralizing antibodies

“…34,35 A hexon-switch experiment would help understand whether anti-fiber NAbs are unique with regard to sero-switching for efficacy, or whether the same might be true for any anti-capsid NAb. 36 Moreover, completely non-Ad5 serotypes might be useful, 13,28,37,38 if the appealing attributes of Ad5 (for example, high gene expression, in vivo stability, easy production, safety) can be retained. This should not be taken for granted, as Ad5 has become the single most popular gene therapy vector because of these attributes, and there is no guarantee that they would apply to other serotypes.…”

Harnessing the Potential of Adenovirus Vectored Vaccines

“…Also, regarding the ability to apply vaccines in manners that will induce local immunosurveillance at the likely site of virus entry or early replication, adenoviral vaccines have been found to be very useful. Thus, studies have suggested that local application can be used to augment mucosal CD8+ T cell memory (Belyakov et al, 2008;de Souza et al, 2007;Kaufman et al, 2010;Lemiale et al, 2007), and also that parenteral immunization can be used to induce T cell homing to mucosal sites (Haut et al, 2010;Kaufman et al, 2010;Lin et al, 2007;Tatsis et al, 2007b). The ability to induce local T cell responses is not a quality unique to adenovirus vectors and local immunity can also be obtained by mucosal application of pox-viral vectors (Corbett et al, 2008).…”