The influence of adjuvant on the therapeutic efficacy of a recombinant genital herpes vaccine.
The potential use of vaccines for treatment of chronic or persistent virus infections is an area of great interest and controversy. Previous experiments have shown that the incidence and severity of spontaneous recurrent genital herpes in latently infected guinea pigs could be significantly reduced by vaccination with herpes simplex virus glycoprotein subunit vaccines. The current study shows the critical role of adjuvant in an effective formulation. Immunization of previously infected guinea pigs with a subunit vaccine containing a muramyl peptide derivative, MTP-PE, in a low-oil emulsion as adjuvant reduced the incidence of recurrent disease up to 80% compared with formulations lacking MPT-PE. Vaccines containing adjuvant alone failed to modify recurrences. Alum, the traditional adjuvant, was not effective. Glycoprotein subunit vaccines elicited high-titer ELISA and neutralizing antibody responses far greater than those generated by virus infection. However, neither antibody titers nor lymphoproliferative responses reproducibly correlated with the pattern of recurrent disease.
Biocine Co, Emeryville, California.
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Burke
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Goldbeck
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Stanberry
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Van Nest
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D008213:Lymphocyte Activation; D010714:Phosphatidylethanolamines / Q000494:pharmacology*; D014614:Vaccines, Synthetic / Q000627:therapeutic use*; D014759:Viral Envelope Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D010714:Phosphatidylethanolamines; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C044525:glycoprotein B, herpes simplex virus type 2; C040570:glycoprotein D-herpes simplex virus type 2; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine