coxsackievirus/HIV recombinant induces

Oral immunization with a live coxsackievirus/HIV recombinant induces gag p24-specific T cell responses.

Gu R, Shampang A, Nashar T, Patil M, Fuller DH, Ramsingh AI. PLoS One. 2010;5(9). pii: e12499.

The development of an HIV vaccine has proven to be elusive. Because human vaccine trials have not yet demonstrated efficacy, new vaccine strategies are needed for the HIV vaccine pipeline. Gu and colleagues have been developing a new HIV vaccine platform using a live enterovirus, coxsackievirus B4 (CVB4) vector. Enteroviruses are ideal candidates for development as a vaccine vector for oral delivery, because these viruses normally enter the body via the oral route and survive the acidic environment of the stomach. The authors constructed a live coxsackievirus B4 recombinant, CVB4/p24(73(3)), that expresses seventy-three amino acids of the gag p24 sequence (HXB2) and assessed T cell responses after immunization of mice. The CVB4 recombinant was physically stable, replication-competent, and genetically stable. Oral or intraperitoneal immunization with the recombinant resulted in strong systemic gag p24-specific T cell responses as determined by the IFN-gamma ELISPOT assay and by multiparameter flow cytometry. Oral immunization with CVB4/p24(73(3)) resulted in a short-lived, localized infection of the gut without systemic spread. Because coxsackieviruses are ubiquitous in the human population, they also evaluated whether the recombinant was able to induce gag p24-specific T cell responses in mice pre-immunized with the CVB4 vector. They showed that oral immunization with CVB4/p24(73(3)) induced gag p24-specific immune responses in vector-immune mice. The CVB4/p24(73(3)) recombinant retained the physical and biological characteristics of the parental CVB4 vector. Oral immunization with the CVB4 recombinant was safe and resulted in the induction of systemic HIV-specific T cell responses. Furthermore, pre-existing vector immunity did not preclude the development of gag p24-specific T cell responses. As the search continues for new vaccine strategies, the present study suggests that live CVB4/HIV recombinants are potential new vaccine candidates for HIV.

Editors’ note: Yes, this study was in mice, not humans, but that is where the study of oral HIV vaccines begins. Given that HIV infection starts as a disease of the mucosal immune system, particularly the gut, that then extends systemically, it makes sense to see if both mucosal and systemic immune responses can be stimulated with an oral vaccine. That is how the oral Sabin vaccine against poliomyelitis works, so why not an oral vaccine for HIV? These are very early days but this study using a coxsackievirus vector (humans mostly have no symptoms when infected by these common viruses) to carry an HIV recombinant expressing gag p24 found that mice expressed gag p24-specific T cell responses after immunization even when they had pre-existing immunity to coxsackievirus. This constitutes proof of principle at the start of a long road ahead.