Effects of DNA immunization formulated with bupivacaine in murine and guinea pig models of genital herpes simplex virus infection.
The immunogenicity and efficacy of a herpes simplex virus type 2 glycoprotein D (gD2) DNA vaccine formulated with bupivacaine was evaluated using murine and guinea pig models of genital herpes. Animals received three doses of 100 microg of gD2 plasmid or control plasmid intramuscularly prior to intravaginal challenge with HSV-2. Immunization induced HSV ELISA and neutralizing antibody in serum and ELISA antibody in the vaginal secretions of all animals evaluated. Following intravaginal HSV-2 challenge, vaginal viral replication was reduced in both models with peak reductions of greater than 99%. Immunization also decreased the number of animals developing any clinical disease (p < 0.001) and the severity of the acute disease (total lesion score 6.4 versus 0.6 in guinea pigs, p < 0.001). Further recurrent lesion days were reduced from 14.5 to 4.9 days in immunized guinea pigs (p < 0.001). DNA immunization with gD2 + bupivacaine was effective in reducing clinical disease and viral replication in both guinea pigs and mice.
Bernstein
D I
DI
Division of Infectious Diseases, Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. dib@chmcc.org
Tepe
E R
ER
Mester
J C
JC
Arnold
R L
RL
Stanberry
L R
LR
Higgins
T
T
D000818:Animals; D000914:Antibodies, Viral / Q000032:analysis* / Q000097:blood; D002045:Bupivacaine / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D009500:Neutralization Tests; D012008:Recurrence; D012867:Skin / Q000821:virology; D013997:Time Factors; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014621:Vagina / Q000276:immunology / Q000821:virology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014779:Virus Replication; D017201:Virus Shedding
D000914:Antibodies, Viral; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C040570:glycoprotein D-herpes simplex virus type 2; D002045:Bupivacaine