Duration of protection from live attenuated vs. sub unit HSV-2 vaccines in the guinea pig model of genital herpes: Reassessing efficacy using endpoints from clinical trials

ABSTRACT The antiviral effect of acyclovir elaidate in the female guinea pig model of genital herpes was investigated in a series of experiments. The antiherpesvirus effects of this novel compound, 9-(2′-[trans-9"-octadecenoyloxyl]ethoxymethyl)guanine (code no. P-4010), were studied in both primary and recurrent genital herpes in the female guinea pig, following oral gavage or intraperitoneal injection, with different formulations of the compound, and in comparison with acyclovir (ACV) or penciclovir (PCV). The results indicate that compound P-4010 has a greater capability than either ACV or PCV in reducing the clinical symptoms of primary genital herpes induced following the inoculation of herpes simplex virus type 2 (HSV-2) intravaginally into guinea pigs. In addition, the administration of P-4010 twice daily over a 10-day period by the intraperitoneal route (15 to 40 mg/kg of body weight/day) or by oral gavage (50 to 200 mg/kg/day), commencing 4 h subsequent to intravaginal HSV-2 infection, resulted in a degree of reduction in the incidence and severity of spontaneous, recurrent genital herpes in these animals. The findings are discussed in the light of the value and relevance of the female guinea pig model of genital herpes for the assessment of anti-herpes simplex virus compounds.

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Superior Efficacy of Helicase-Primase Inhibitor BAY 57–1293 for Herpes Infection and Latency in the Guinea Pig Model of Human Genital Herpes Disease

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632020701800104 ◽

2007 ◽

Vol 18 (1) ◽

pp. 35-48 ◽

Cited By ~ 34

Author(s):

Judith Baumeister ◽

Ruediger Fischer ◽

Peter Eckenberg ◽

Kerstin Henninger ◽

Helga Ruebsamen-Waigmann ◽

...

Keyword(s):

Guinea Pig ◽

Genital Herpes ◽

Pig Model ◽

Herpes Infection ◽

Superior Efficacy ◽

Guinea Pig Model

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Evaluations of Unformulated and Formulated Dendrimer-Based Microbicide Candidates in Mouse and Guinea Pig Models of Genital Herpes

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.47.12.3784-3788.2003 ◽

2003 ◽

Vol 47 (12) ◽

pp. 3784-3788 ◽

Cited By ~ 74

Author(s):

D. I. Bernstein ◽

L. R. Stanberry ◽

S. Sacks ◽

N. K. Ayisi ◽

Y. H. Gong ◽

...

Keyword(s):

Guinea Pig ◽

Genital Herpes ◽

Significant Protection ◽

Sexually Transmitted ◽

Cost Efficient ◽

Guinea Pig Model ◽

Simplex Virus ◽

Duration Of Protection

ABSTRACT Prevention of sexually transmitted infections is a priority in developed and developing countries. One approach to prevention is the use of topical microbicides, and one promising approach is the use of dendrimers, highly branched macromolecules synthesized from a polyfunctional core. Three new dendrimer products developed to provide stable and cost-efficient microbicides were initially evaluated in vitro for anti-herpes simplex virus activity and then in vivo by using a mouse model of genital herpes. From these experiments one product, SPL7013, was chosen for further evaluation to define the dose and duration of protection. Unformulated SPL7013 provided significant protection from genital herpes disease and infection at concentrations as low as 1 mg/ml and for at least 1 h following topical (intravaginal) administration of 10 mg/ml. This compound was then formulated into three vehicles and further evaluated in mouse and guinea pig models of genital herpes infection. In the murine evaluations each of the formulations provided significant protection at concentrations of 10 and 50 mg/ml. Formulated compounds provided protection for at least 1 h at a concentration of 10 mg/ml. From these experiments formulation 2V was chosen for dose ranging experiments using the guinea pig model of genital herpes. The guinea pig evaluations suggested that doses of 30 to 50 mg/ml were required for optimal protection. From these studies a lead compound and formulation (2V of SPL7013) was chosen for ongoing evaluations in primate models of simian immunodeficiency virus and Chlamydia trachomatis infection.

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