Details

Autor(en) / Beteiligte

• Hoshino, Yo
• Pesnicak, Lesley
• Dowdell, Kennichi C
• Lacayo, Juan
• Dudek, Timothy
• Knipe, David M
• Straus, Stephen E
• Cohen, Jeffrey I

Titel

Comparison of immunogenicity and protective efficacy of genital herpes vaccine candidates herpes simplex virus 2 dl 5-29 and dl 5-29-41L in mice and guinea pigs

Ist Teil von

• Vaccine, 2008, Vol.26 (32), p.4034-4040

Erscheinungsjahr

2008

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Abstract A replication-defective herpes simplex virus (HSV)-2 vaccine, dl 5-29, which is deleted for two essential early genes, UL5 and UL29, is highly immunogenic and protective in mice and guinea pigs. In a prior study, a derivative of HSV-2 dl 5-29 termed dl 5-29-41L, which has an additional deletion in UL41 (that encodes the virion-host shut-off protein), was more immunogenic and protective against challenge with wild-type HSV-2 in mice when compared with dl 5-29. To determine if deletion of UL41 improves the efficacy of dl 5-29 in protecting guinea pigs from HSV-2, animals were immunized with dl 5-29, dl 5-29-41L, or PBS. The geometric mean neutralizing antibody titers from the dl 5-29 and dl 5-29-41L recipients were comparable (101.97 and 102.19 , respectively, p = 0.15). After intravaginal challenge with wild-type HSV-2, the dl 5-29-41L and dl 5-29 recipients shed similar titers of HSV-2 from the vagina. Mean acute disease severity scores, numbers of recurrences during 3 months after infection, and latent viral loads in sacral ganglia were similar for dl 5-29 and dl 5-29-41L (all p values >0.05). dl 5-29 and dl 5-29-41L completely protected mice from lethal challenge with HSV-2 and induced virus-specific CD8+ T cells in the spleens of the animals. Thus, dl 5-29 was as immunogenic and protective as dl 5-29-41L under these conditions. dl 5-29 was at least 250,000-fold less virulent than parental virus by intracranial inoculation in healthy mice, and caused no disease in SCID mice. Both dl 5-29-41L and dl 5-29 are equally effective and immunogenic in guinea pigs, and dl 5-29 is very safe in immunocompromised animals.