Vaccine-induced serum immunoglobin contributes to protection from herpes simplex virus type 2 genital infection in the presence of immune T cells

Herpes simplex type virus 2 (HSV-2) is a sexually transmitted pathogen that causes genital lesions and spreads to the nervous system to establish acut e and latent infections. Systemic but not mucosal cellular and humoral immu ne responses are elicited by immunization of mice with a replication-defect ive mutant of HSV-2, yet the mice are protected against disease caused by s ubsequent challenge of the genital mucosa with virulent HSV-2. In this stud y, we investigated the role of immune serum antibody generated by immunizat ion with a replication defective HSV-2 vaccine prototype strain in protecti on of the genital mucosa and the nervous system from HSV-2 infection. Passi ve transfer of replication-defective virus-immune serum at physiologic conc entrations to SCID or B-cell-deficient mice had no effect on replication of challenge virus in the genital mucosa but did significantly reduce the inc idence and severity of genital and neurologic disease. In contrast, B cell- deficient mice immunized with replication-defective HSV-2 were able to cont rol replication of challenge virus in the genital mucosa, but not until 3 d ays postchallenge, and were not completely protected against genital and ne urologic disease. Passive transfer of physiologic amounts of immune serum t o immunized, B-cell-deficient mice completely restored their capacity to li mit replication of challenge virus in the genital mucosa and prevented sign s of genital and systemic disease. In addition, the numbers of viral genome s in the lumbosacral dorsal root ganglia of immunized, B-cell-deficient mic e were dramatically reduced by transfer of immune serum prior to challenge. These results suggest that there is an apparent synergism between immune s erum antibody: and immune T cells in achieving protection and that serum an tibody induced by vaccination with replication-defective virus aids in redu cing establishment of latent infection after genital infection with HSV-2.