Vaccines and Microbicides Preventing HIV-1, HSV-2, and HPV Mucosal Transmission

Abstract

HIV-1, herpes simplex virus type 2 (HSV-2), and human papillomavirus (HPV), among other sexually transmitted infections, represent a major burden for global health. Initial insights into the mucosal transmission of these viral pathogens have raised optimism with regard to the rapid generation of protective vaccines. Nevertheless, setbacks for HIV-1 and HSV-2 vaccines have seriously challenged the initial enthusiasm. Recently, two new vaccines that efficiently prevented HPV infection have renewed the hope that vaccinal prevention of viral mucosal sexually transmitted infections is possible. HIV-1 and HSV-2 differ from HPV, and each virus needs to be tackled with a distinct approach. However, vaccines are not the only possible answer. Topically applied agents (microbicides) are an attractive alternative in the prevention of HIV-1 and HSV-2 mucosal transmission. Progress in understanding the mechanisms of genital transmission of HIV-1 and HSV-2 is required for successful vaccine or microbicide candidates to emerge from current approaches.

A Lentiviral Vector-Based, Herpes Simplex Virus 1 (HSV-1) Glycoprotein B Vaccine Affords Cross-Protection against HSV-1 and HSV-2 Genital Infections

“…Even more disappointingly, vLAW-gB1/RD afforded no protection against HSV-1 challenge. In contrast, the vLAW-gB1/VSV vaccinees were fully protected from disease, paralleling the results obtained from most HSV vaccines hitherto developed (17,38).…”

“…In general, these vaccines, whether tested in animal models or clinical studies, prevented HSV-1 disease but were poorly protective against lethal doses of HSV-1 and were clearly inadequate against HSV-2. The studies also showed that mucosal immunity is important to prevent or curb the course of infection (17,27,30,38).…”

“…Despite many efforts in vaccine development and several clinical tests (5,14,27), no truly effective measures to prevent infection or disease are currently available (17,38).…”

“…Since LAW34 can stably deliver two or more genes for up to 7 kb of heterologous DNA (61), this vaccine has ample room for improvement. Indeed, we are already testing in vitro LAW34 delivering gB and gD, another HSV receptor extensively used for vaccination (17,38,65), and gB and ICP27, a multifunctional early regulatory protein eliciting strong and protective cell-mediated immune responses (32). With a truly protective vaccine years away (5), LAW34, either administered alone or combined with other delivery systems, may become a structural component of an effective vaccine against the genital herpes.…”

A look at HIV journey

“…Alternative strategies have emerged, with the use of microbicides, aimed at targeting and preventing specific steps of viral transmission upon mucosal surfaces challenge by HIV-1 (reviewed in [43]). …”