The effect of adjuvants on the efficacy of a recombinant herpes simplex virus glycoprotein vaccine.
A recombinant, truncated HSV type 1 glycoprotein D secreted by Chinese hamster ovary cells (rgD1) was used to compare the ability of several adjuvants to stimulate protective immunity in guinea pigs. Adjuvants tested included CFA, aluminum hydroxide (alum), a lipophilic derivative of muramyl tripeptide (MTP-PE), and a muramyl dipeptide (MDP) covalently conjugated to rgD1. Animals were immunized three times with rgD1 plus the various adjuvants and antibody titers were determined by ELISA. Four weeks after the last immunization, the animals were challenged intravaginally with HSV type 2 and were monitored daily for clinical signs of disease, including frequency and severity of herpetic lesions, incidence of urinary retention, and mortality during the 14-day post-challenge observation period. Animals immunized in the foot-pad with rgD1 formulated with CFA showed the highest antibody titers. Animals immunized in the footpad with rgD1 using MTP-PE in a 4% squalene formulation, alum, or rgD1 conjugated to MDP showed mean antibody titers that were 57, 16, and 13% of the CFA titers, respectively. Immunization with rgD1 plus MTP-PE, alum, or rgD1-MDP conjugate by the i.m. route elicited lower antibody titers than the footpad route of immunization. Results of the viral challenge indicated that clinical symptoms of the groups immunized with rgD1 with CFA or MTP-PE as adjuvant were similar in magnitude and were markedly reduced compared with unimmunized control groups. Animals immunized with rgD1 combined with alum or rgD1-MDP conjugate showed clinical symptoms significantly more severe than the CFA or MTP-PE groups. The protective immunity observed after i.m. immunization of animals with rgD1 and MTP-PE was only slightly lower than animals immunized with the same Ag-adjuvant combination in the footpad. The results indicate that MTP-PE is an effective adjuvant for the recombinant herpes gD vaccine.
Sanchez-Pescador
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Chiron Corporation, Emeryville, CA 94608.
Burke
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RL
Ott
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Van Nest
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D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds; D000535:Aluminum / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000941:Antigens / Q000627:therapeutic use*; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology; D006168:Guinea Pigs; D006561:Herpes Simplex / Q000517:prevention & control; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000627:therapeutic use*; D018139:Simplexvirus / Q000276:immunology*; D013431:Sulfates / Q000494:pharmacology; D014614:Vaccines, Synthetic / Q000276:immunology / Q000627:therapeutic use*; D014759:Viral Envelope Proteins / Q000276:immunology / Q000627:therapeutic use*
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000914:Antibodies, Viral; D000941:Antigens; D010714:Phosphatidylethanolamines; D011994:Recombinant Proteins; D013431:Sulfates; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C037144:mifamurtide; C041524:aluminum sulfate; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D005620:Freund's Adjuvant; D000535:Aluminum