Protection from herpes simplex virus (HSV)-2 infection with replication-defective HSV-2 or glycoprotein D2 vaccines in HSV-1-seropositive and HSV-1-seronegative guinea pigs.
BACKGROUND
A herpes simplex virus (HSV)-2 candidate vaccine consisting of glycoprotein D (gD2) in alum and monophosphoryl lipid A (MPL) reduced genital herpes disease in HSV-1-seronegative women but not in men or HSV-1-seropositive women.


METHODS
To determine the effect of HSV-1 serostatus on effectiveness of different vaccines, we tested gD2 in alum/MPL, gD2 in Freund's adjuvant, and dl5-29 (a replication-defective HSV-2 mutant) in HSV-1-seropositive or HSV-1-seronegative guinea pigs.


RESULTS
In HSV-1-seronegative animals, dl5-29 induced the highest titers of neutralizing antibody, and after vaginal challenge with wild-type virus, dl5-29 resulted in lower rates of vaginal shedding, lower levels of HSV DNA in ganglia, and a trend for less acute and recurrent genital herpes, compared with the gD2 vaccines. In HSV-1-seropositive animals, all 3 vaccines induced similar titers of neutralizing antibodies and showed similar levels of protection against acute and recurrent genital herpes after vaginal challenge with wild-type virus, but dl5-29 reduced vaginal shedding after challenge more than did the gD2 vaccines.


CONCLUSIONS
dl5-29 Is an effective vaccine in both HSV-1-seropositive and HSV-1-seronegative guinea pigs and was superior to gD2 vaccines in reducing virus shedding after challenge in both groups of animals. dl5-29 Might reduce transmission of HSV-2.
Hoshino
Yo
Y
Medical Virology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Pesnicak
Lesley
L
Dowdell
Kennichi C
KC
Burbelo
Peter D
PD
Knipe
David M
DM
Straus
Stephen E
SE
Cohen
Jeffrey I
JI
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000517:prevention & control*; D018259:Herpesvirus 1, Human / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D012008:Recurrence; D014613:Vaccines, Attenuated / Q000276:immunology*; D014621:Vagina / Q000821:virology; D014759:Viral Envelope Proteins / Q000276:immunology; D019562:Viral Load; D014765:Viral Vaccines / Q000276:immunology*; D017735:Virus Latency; D014779:Virus Replication; D017201:Virus Shedding
D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; D014765:Viral Vaccines
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