Protection against lethal challenge of BALB/c mice by passive transfer of monoclonal antibodies to five glycoproteins of herpes simplex virus type 2

Abstract

Monoclonal antibodies secreted by six hybridomas and recognizing antigenic sites on glycoproteins gC, gAB, gD, gE, and gF of herpes simplex virus type 2 were examined for their ability to protect BALB/c mice from lethal infection by the virus. Administration of monoclonal antibodies to individual glycoproteins intraperitoneally 3 h before footpad challenge with 10 times the 50% lethal dose of virus protected between 35 and 75% of the mice, except for one of two monoclonal antibodies recognizing antigens on gC. The antibodies did not neutralize virus in vitro and protected A/J mice deficient in the fifth component of complement as efficiently as complement-sufficient BALB/c mice. A good correlation was found between protection and titers of monoclonal antibodies assessed by antibody-dependent cell-mediated cytolysis. The results indicate that any of the glycoproteins can serve as antigens for a protective immune response. In addition, the data are compatible with protection being mediated by an antibodydependent cell-mediated cytolysis mechanism.

Recombinant Vesicular Stomatitis Virus Vectors Expressing Herpes Simplex Virus Type 2 gD Elicit Robust CD4+Th1 Immune Responses and Are Protective in Mouse and Guinea Pig Models of Vaginal Challenge

“…Furthermore, we have previously demonstrated that gD subunit immunization (without adjuvants) elicits neutralizing antibodies without the induction of a detectable CD4 ϩ CTL response and still protects mice from HSV-2 vaginal challenge (9). In addition, the ability of anti-gD antibodies to protect mice in the absence of a cellular response was demonstrated by a number of passive transfer studies with monoclonal anti-gD antibodies (2,23,55,68,71). Moreover, it was shown that the Th1-like IgG2a monoclonal anti-gD antibody was superior to the IgG1 monoclonal anti-gD antibody with regard to the relative efficacy of the passive protection conferred (24).…”

The antiviral activity of antibodies in vitro and in vivo

“…Many studies have looked at the ability of mAbs to protect against HSV infection. Early papers showed that both neutralizing anti-gD and gC mAbs and nonneutralizing anti-gD, gC, gB, gD, and gE mAbs could protect against lethal footpad challenge in mice (Balachandran et al, 1982;Dix et al, 1981). The latter study found that a mixture of mAbs had an efficacy corresponding roughly to the sum of that of the individual mAbs and that protection was equally apparent in C5-deficient mice.…”

Vaccine induced HSV 1 antibodies fail to correlate with protection against HSV 2 in guinea pigs

“…Attempts have been made to correlate the ability to protect with activity and in vitro functional assays, i.e., antibody and complement-mediated cytotoxicity (CMC), antibody-dependent cellular cytotoxicity (ADCC), and neutralization with or without complement. However, such associations have not been conclusively demonstrated [3][4][5]. In the present study we vaccinated guinea pigs with a HSV 1 subunit vaccine [6], and subsequently challenged them intravaginally with HSV 2.…”