A mucosal vaccination approach for herpes simplex virus type 2.
An estimated 1 out of every 5 Americans is infected with herpes simplex virus type 2 (HSV-2). Efforts in developing a potent vaccine for HSV-2 have shown limited success. Here we describe a heterologous vaccination strategy for HSV-2 based on an intramuscular DNA prime followed by a liposome-encapsulated antigen boost delivered intranasally. Both portions of the vaccine express the immunogenic HSV-2 glycoprotein D. In female Balb/c mice, this heterologous immunisation regimen stimulated high titers of serum neutralising antibodies, a DNA priming dose dependent T helper type response, enhanced mucosal immune responses and potent protective immunity at the portal of entry for the virus: the vaginal cavity. A clear synergistic effect on immune responses and protection from infection was seen using this heterologous immunisation approach. Suboptimal DNA prime (0.5 μg) followed by the liposome boost resulted in an 80% survival rate when mice were infected 2 weeks after immunisation. A higher dose of DNA priming (5 μg) followed by the liposome boost resulted in sterilising immunity in 80% of mice. The vaccine induced durable protection in mice, demonstrated by a 60% survival rate when lethal infections were performed 20 weeks after the immunisation primed with 0.5 μg of DNA vaccine.
Biomedical Research Models, Inc., 67 Millbrook Street, Suite 422, Worcester, MA 01606, USA.
Rebecca S
RS
Tirabassi
Christopher I
CI
Ace
Tatyana
T
Levchenko
Vladimir P
VP
Torchilin
Liisa K
LK
Selin
Siwei
S
Nie
Dennis L
DL
Guberski
Kejian
K
Yang
D058956:Administration, Mucosal; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D022301:Herpes Simplex Virus Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D018258:Herpesvirus 2, Human / Q000276:immunology*; D018928:Immunity, Mucosal; D007117:Immunization, Secondary / Q000379:methods*; D007273:Injections, Intramuscular; D051379:Mice; D008807:Mice, Inbred BALB C; D016019:Survival Analysis; D013997:Time Factors; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014621:Vagina / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022301:Herpes Simplex Virus Vaccines; D019444:Vaccines, DNA; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2