Comparative efficacy and immunogenicity of replication-defective, recombinant glycoprotein, and DNA vaccines for herpes simplex virus 2 infections in mice and guinea pigs.
Many candidate vaccines are effective in animal models of genital herpes simplex virus type 2 (HSV-2) infection. Among them, clinical trials showed moderate protection from genital disease with recombinant HSV-2 glycoprotein D (gD2) in alum-monophosphoryl lipid A adjuvant only in HSV women seronegative for both HSV-1 and HSV-2, encouraging development of additional vaccine options. Therefore, we undertook direct comparative studies of the prophylactic and therapeutic efficacies and immunogenicities of three different classes of candidate vaccines given in four regimens to two species of animals: recombinant gD2, a plasmid expressing gD2, and dl5-29, a replication-defective strain of HSV-2 with the essential genes UL5 and UL29 deleted. Both dl5-29 and gD2 were highly effective in attenuating acute and recurrent disease and reducing latent viral load, and both were superior to the plasmid vaccine alone or the plasmid vaccine followed by one dose of dl5-29. dl5-29 was also effective in treating established infections. Moreover, latent dl5-29 virus could not be detected by PCR in sacral ganglia from guinea pigs vaccinated intravaginally. Finally, dl5-29 was superior to gD2 in inducing higher neutralizing antibody titers and the more rapid accumulation of HSV-2-specific CD8+ T cells in trigeminal ganglia after challenge with wild-type virus. Given its efficacy, its defectiveness for latency, and its ability to induce rapid, virus-specific CD8(+)-T-cell responses, the dl5-29 vaccine may be a good candidate for early-phase human trials.
Hoshino
Yo
Y
Medical Virology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, Maryland 20892, USA.
Dalai
Sarat K
SK
Wang
Kening
K
Pesnicak
Lesley
L
Lau
Tsz Y
TY
Knipe
David M
DM
Cohen
Jeffrey I
JI
Straus
Stephen E
SE
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D006168:Guinea Pigs; D006558:Herpes Genitalis / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D051379:Mice; D010957:Plasmids; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics; D014764:Viral Proteins / Q000235:genetics; D014779:Virus Replication
D022301:Herpes Simplex Virus Vaccines; C413084:UL29 protein, Herpes simplex virus type 2; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C040570:glycoprotein D-herpes simplex virus type 2