Immune inhibition of virus release from human and nonhuman cells by antibody to viral and host cell determinants.

Immune inhibition of release of the DNA viruses, herpes simplex virus types 1 and 2 and pseudorabies virus by anti-viral and anti-host cell sera occurred while two RNA viruses, influenza and encephalomyocarditis, were inhibited only by anti-viral sera (not anti-host cell sera). Simian virus 40 and surprisingly two herpes viruses, bovine mamillitis and equine abortion, were not inhibited by either anti-viral or anti-host sera. Using the herpes simplex virus model, inhibition of virus release was detected in different cells of human and nonhuman origin with cross-inhibition between cell lines of different origin; thus, this form of immunotherapy may not require antibody to be tissue or organ specific. Evidence of inhibition of virus release from neoplastic and leukemic cell lines suggests possible application of this approach to control of virus-mediated leukoproliferative pathology (e.g. Burkitt's lymphoma or adult T cell leukemia).

Immune inhibition of virus release from herpes simplex virus-infected cells by human sera.

Human sera contain antibody (IVR antibody) which will inhibit the release of herpes simplex virus type 1 from virus-infected cells. This antibody activity was removed by adsorption of sera with virus-infected cell extract. There was a positive correlation between IVR and neutralizing antibody activity, particularly when measured by augmented neutralization test; measurement of IVR antibody was equally as sensitive as measurement of neutralizing antibody by augmented neutralization test. IVR antibody levels provided indication of a history of recurrent herpes labialis, the pattern of antibody response following primary herpetic infection, and indication of response to Skinner herpes vaccine in human subjects. It is suggested that consideration should be given to measurement of IVR antibody in both clinical and epidemiological studies of herpes and other virus infections.

Humoral antibody response in patients with herpes genitalis: analysis of factors influencing the pattern of disease.

An investigation was made of the diagnosis of herpes genitalis, the prediction of virus type and the likelihood and frequency of clinical and asymptomatic recurrences in relation to a history of herpes labialis, the virus type isolated from genital lesions and the humoral antibody status against HSV 1 and 2. Diagnosis of herpes genitalis correlated negatively with mean neutralising antibody levels against HSV type 1 and type 2 but positively with the variance of neutralising antibody levels in sequential sera. Virus type in patients with initial episodes was best predicted by initial and mean type 2 antibody levels and in patients with recurrent disease by the ratio of type 1 to type 2 antibody by radioimmune assay. The likelihood and frequency of clinical and asymptomatic recurrences was higher in patients where HSV type 2 was isolated. The likelihood of recurrences in patients with initial episodes was related to high initial neutralising antibody levels against type 2 and to low primary antibody responses against type 1 while frequency of recurrences was best related to low initial antibody levels against type 1 in combination with high levels against type 2. These data will be useful in diagnosis of herpes genitalis. Prediction of the likelihood and frequency of clinical and asymptomatic recurrences will facilitate advice concerning prognosis and risk factors to patients and their consorts.

Antibody reactivity with Skinner HSV vaccine.

Antibody reactivity against herpes simplex virus (HSV) was investigated in 15 subjects who received three subcutaneous immunisations with Skinner HSV vaccine. Humoral antibody responses were detected against type 1 HSV in every subject and against type 2 HSV in all but one subject; immuno-precipitating antibody responses were infrequently detected. There was no antibody reactivity against host-cell (MRC-5), foetal calf serum or rubella virus antigen. None of the vaccinated subjects developed clinical evidence of herpes genitalis.

Irreproducibility of neutralization of herpes simplex virus under conditions where antibody is not in excess.

Neutralizing activity against herpes simplex virus was significantly reduced if initial virus titers were greater than 10(6) PFU/ml; there was no significant neutralization when initial virus titers approached 10(8) PFU/ml. This was a result of utilization of all available antibody by virus particles and 'free' virus antigen and emphasizes the importance of conducting virus neutralization tests under conditions of antibody excess.