-to improve the immunogenicity and efficacy of a gD2-based subunit antigen vaccine by inducing potent immunity to three antigens, two of which prevent HSV immune evasion from antibody and complement. 

- gE2 is a candidate antigen for inclusion in a multivalent subunit vaccine that attempts to block HSV-2 immune evasion.
-when gE2 was added to gC2/gD2 to form a trivalent vaccine, neutralizing antibody titers with and without complement were significantly higher than those produced by gD2 alone. 
-Our results indicate that gE2 functions in synergy with gC2 to protect the virus from antibody and complement neutralization. The addition of gE2 to a gC2/gD2 subunit antigen vaccine provides strong protection against HSV-2 vaginal challenge, preventing death and genital disease, and a high level of protection to lumbosacral dorsal root ganglia (DRG), which serve as the site of HSV-2 latency.

-HIV-1 and HSV-2 coinfections are very common. HSV-2, as the main source of genital ulcers, can facilitate HIV-1 transmission (reviewed in Freeman et al., 2006)
-HSV-2 reactivation at the genital level can stimulate HIV-1 replication (Schacker et al., 1998)
-Treatment of HSV-2 infection with valacyclovir dramatically reduces genital and plasma HIV-1 mRNA levels (Nagot et al., 2007).
-Currently, the two established prevention methods for HSV-2 transmission are condoms (Wald et al., 2005) and HSV-2 antiviral treatment (Corey et al., 2004).
- At present, only two HSV-2 vaccines have successfully completed phase III clinical trials(Figure 1).
-The first one contains HSV-2 surface glycoproteins gB and gD, combined with the adjuvant MF59, known to induce T helper cell type 2 (Th2) responses.
-However, this trial showed no protection against HSV-2 acquisition and occurrence of genital ulcers, despite the elicitation of relatively high titers of neutralizing antibodies (Corey et al., 1999).
-The second candidate vaccine combined the truncated glycoprotein gD2 with the adjuvant aluminum hydroxide linked to MPL (alu-MPL), a known inducer of Th1 responses.
-A good level of protection was achieved with this vaccine, but only in HSV-2-seronegative women (Stanberry et al., 2002).
-In conclusion, the HSV-2 vaccine field still faces some major immunological issues.
-Another type of microbicide against HSV-2 aims at blocking viral entry into host cells, keratinocytes, and neurons. PRO 2000 and cellulose sulfate are sulfated polymers that interact with HIV-1 gp120 and with HSV-2 gB, thereby preventing HIV-1 as well as HSV-2 entry into target cells (Cheshenko et al., 2004).
-A combination of Carraguard and zinc was investigated by the Population Council. This compound, named PC-710, showed greater efficiency of HSV-2 protection in animal models when compared with HIV-1 protection. It may therefore serve as a microbicide against HSV-2, but its lack of activity against HIV-1 in clinical trials is a matter of concern (Skoler-Karpoff et al., 2008).

3. Topical microbicides for the prevention of genital 🤬 infection

-  compounds that prevent entry into target cells may be most advantageous. PRO 2000, Carraguard, polystyrene sulphonate and cellulose sulphate are sulphated or sulphonated polymers that interact directly with viral envelope glycoproteins (including glycoprotein B of HSV-2 and gp120 of HIV) and competitively inhibit viral attachment and prevent entry.²⁰ These products exhibit little or no cytotoxicity even at high doses, do not disrupt normal vaginal flora and do not induce a significant inflammatory response. However, the concentration of SLPI, which may be important in protecting the host from HIV and HSV, is substantially reduced following acute or chronic exposure of human epithelial cells to sulphonated/sulphated polymers in vitro.²⁰ It remains to be determined whether the reduction of SLPI observed in vitro would increase susceptibility to HSV, HIV or other STI. A potential limitation of this class of compounds is that they do not actually 🤬 the pathogen, and thus optimally might be used in combination with other candidate agents. Several of these compounds are in Phase II or III clinical trials.

Once the virus enters through the skin it travels along nerve paths. It may become dormant (inactive) in the nerves and remain there indefinitely.

Blister on infected area

In vivo (Latin for “within the living”) refers to experimentation using a whole, living organism as opposed to a partial or dead organism. Animal studies and clinical trials are two forms of in vivo research. In vivo testing is often employed over in vitro because it is better suited for observing the overall effects of an experiment on a living subject.