Herpes simplex type 2 virus deleted in glycoprotein D protects against vaginal, skin and neural disease

eLife

Natalia Cheshenko¹  Betsy C Herold¹  Nazanin Khajoueinejad²  Pablo A González²  Angèle Bénard³  Christopher Petro⁴  William R Jacobs Jr⁴  Thomas Jandl⁴  Mayami Sengupta⁴ 

[1] Department of Pediatrics, Albert Einstein College of Medicine, New York, United States;Howard Hughes Medical Institute, Albert Einstein College of Medicine, New York, United States;Millennium Institute on Immunology and Immunotherapy, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile;Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, United States;

关键词: vaccine;    HSV-2;    virology;    antibody;    immunity;   

DOI  :  10.7554/eLife.06054

来源: DOAJ

【 摘 要 】

Subunit vaccines comprised of glycoprotein D (gD-2) failed to prevent HSV-2 highlighting need for novel strategies. To test the hypothesis that deletion of gD-2 unmasks protective antigens, we evaluated the efficacy and safety of an HSV-2 virus deleted in gD-2 and complemented allowing a single round of replication on cells expressing HSV-1 gD (ΔgD−/+gD−1). Subcutaneous immunization of C57BL/6 or BALB/c mice with ΔgD−/+gD1 provided 100% protection against lethal intravaginal or skin challenges and prevented latency. ΔgD−/+gD1 elicited no disease in SCID mice, whereas 1000-fold lower doses of wild-type virus were lethal. HSV-specific antibodies were detected in serum (titer 1:800,000) following immunization and in vaginal washes after intravaginal challenge. The antibodies elicited cell-mediated cytotoxicity, but little neutralizing activity. Passive transfer of immune serum completely protected wild-type, but not Fcγ-receptor or neonatal Fc-receptor knock-out mice. These studies demonstrate that non-neutralizing Fc-mediated humoral responses confer protection and support advancement of this attenuated vaccine.

【 授权许可】

Unknown