Characterization and immunogenicity of a candidate subunit vaccine against varicella-zoster virus.

This study describes the properties of an inactivated subunit antigen preparation from varicella-zoster virus (VZV)-infected MRC-5 cells by treatment with detergent and formaldehyde, ultracentrifugation over sucrose and acetone precipitation. The method preserved the antigenicity of VZV proteins and several VZV-specific glycoproteins, while virus DNA was less than 20 pg/250 micrograms protein--a putative vaccine dose. The vaccine was immunogenic in rabbits and stimulated antibodies to the major capsid protein as well as to glycoproteins; an immunoprecipitin was shared with a known immune human serum. The preparation contained no infectious VZV with no evidence of side effects in a rabbit or in five human vaccinees during a follow-up period of 6-10 years.

Report of twelve years experience in open study of Skinner herpes simplex vaccine towards prevention of herpes genitalis.

Three hundred and forty-seven subjects at risk for herpes genitalis were vaccinated with Skinner vaccine, NFUAc.HSV1.(S-MRC5), and were followed for an average duration of 2 years representing a total consortship of 664.4 years. Based on survey information obtained during this consortship, there were estimated to be 3076 recurrences which summated to 3.5 years total duration of disease and comprised at least 6794 lesions; there were an estimated 51997 episodes of intercourse including at least 241 episodes of unprotected intercourse in the presence of herpetic lesions. The rate of contraction of herpes genitalis was 6 of 54 consorts (11.1%) who received one vaccination and 7 of 293 (2.4%) who received two, three of four vaccinations. There was no evidence of physical or psychological side effects from vaccination.

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.

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.

Control of herpes simplex virus infections of the genital tract by vaccination.

The apparent increasing incidence of herpes simplex virus infections of the genital tract has focused attention on the efficacy of vaccination in preventing infection or modifying established disease. Results of an 'open trial' using a DNA-free inactivated virus subunit vaccine have shown that vaccination of subjects at risk of contracting infection from their sexual partner reduced the transmission rate from 34% in unvaccinated controls to 0.5%. In a separate study, vaccination of patients who had experienced their first overt attack of herpes genitalis (the initial clinical episode) had significantly fewer recurrences over the follow-up period of 12 months than the unvaccinated control group. The results, we feel, justify a placebo controlled trial.

Augmentation of the neutralisation test for type 1 HSV: evidence of high representation of neutralising antibody in the adult community.

Optimal neutralisation of type 1 herpes simplex virus was obtained by reacting undiluted human serum with virus for 4 h at 37 degrees C, followed by addition of antihuman globulin for 20 min; under these conditions it was possible to detect neutralising antibody activity in 40 of 45 human sera (88%) previously adjudged to be negative by conventional neutralisation tests.

Non-specificity of surfactant deficiency in neonatal respiratory disorders.

The phospholipid content of lung fluid taken from 77 babies during the first day of life was studied. Babies with hyaline membrane disease had low concentrations of the surfactant phospholipids phosphatidylcholine, phosphatidylinositol, and phosphatidylglycerol. The palmitic acid content in phosphatidylcholine was also lower than normal. Surfactant deficiency was not, however, specific for hyaline membrane disease, as similar phospholipid abnormalities were observed in babies with congenital pneumonia and transient tachypnoea of the newborn. These findings have important clinical implications. They are relevant to research into surfactant substitution and cast doubts on the value of the antenatal phospholipid lung profile of amniotic fluid in predicting the risk of hyaline membrane disease.