Evaluation of AD472, a live attenuated recombinant herpes simplex virus type 2 vaccine in guinea pigs.
An attenuated recombinant herpes simplex virus type 2 (HSV-2), designated as AD472, was constructed by deleting both copies of the gamma(1)34.5 gene, UL55-56, UL43.5, and the US10-12 region from HSV-2 strain G. This virus was engineered to be a safe and effective live attenuated HSV-2 vaccine and was tested in the guinea pig model of genital herpes to evaluate its ability to protect from disease upon challenge with the wild type (wt) virus, HSV-2 (G). AD472 administered intramuscularly did not prevent infection or virus replication in the vaginal tract, but did reduce both lesion development and severity in a dose-dependent manner in guinea pigs challenged with the wt virus. Frequency of reactivation from latency was low compared with that of the parent virus, HSV-2 (G). Immunization with AD472 at doses of 1x10(5)PFU generally precluded colonization of the ganglia or establishment of latency by the challenge virus. Results presented here support the concept of a rationally engineered live attenuated vaccine for the prevention of the genital disease associated with infection by HSV-2.
Prichard
Mark N
MN
Medlmmune Vaccines Inc., 297 N Bernardo Avenue, Mountain View, CA 94043, USA.
Kaiwar
Ravi
R
Jackman
Winthrop T
WT
Quenelle
Debra C
DC
Collins
Deborah J
DJ
Kern
Earl R
ER
Kemble
George M
GM
Spaete
Richard R
RR
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000473:pathology / Q000517:prevention & control / Q000821:virology; D022301:Herpes Simplex Virus Vaccines / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D006801:Humans; D009500:Neutralization Tests; D010641:Phenotype; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014621:Vagina / Q000473:pathology / Q000821:virology; D014779:Virus Replication
D000914:Antibodies, Viral; D022301:Herpes Simplex Virus Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic