Clinical efficacy of a herpes simplex subunit vaccine.

A DNA-free herpes simplex type 2 subunit vaccine was administered to 18 volunteers without past evidence of herpes simplex type 1 (HSV 1) or herpes simplex type 2 (HSV 2) infection, to 44 patients with severe recurrent genital HSV 2 infection, and to 15 patients with severe oral type 1 HSV recurrences. The vaccine elicited both humoral and cell-mediated immunity in 97% of the subjects without past HSV infections and boosted significantly the cell-mediated immunity and antibody titers in almost all the patients with recurrent HSV 1 or HSV 2. The vaccine elicited particularly the production of complement-dependent cytotoxic antibodies in 96% of the patients with recurrent HSV 2 infections. This might, at least partly, explain the clinical efficacy of the vaccine. Indeed, we observed a significant decrease (t test, p less than 0.01) in the attack rate of the recurrences and also a significant shortening of the time needed to complete healing of the lesions (t test, p less than 0.01).

Effect of thymopentin on the mortality and immune response after an experimental herpes simplex infection in mice.

The effect of thymopentin on the mortality rate of mice treated with lethal doses (LD90) of herpes virus 2 and on the cytotoxic T cell activity after sublethal doses (LD10) of herpes virus was investigated in two series of experiments. Doses of 1, 0.1 or 0.01 ng of thymopentin per g/mouse were administered i.p. in each experiment, either 3 days before, 3 days (66 h) after, or 3 and 6 days after the herpes virus infection. The cumulative mortality rate was evaluated 10 days after the infection. Cytotoxic T cell activity was measured 3, 7 and 14 days after the infection. The 0.1-ng dose of thymopentin reduced the mortality rate to less than 50% (p = 0.0000) if it was administered 3 days before the infection. A single injection of any dose after infection did not reduce the mortality at all, while two injections of 0.1 ng reduced it by about 25% (p = 0.0038). A 1-ng dose showed a mild but significant reduction (p = 0.0313) if it was applied 3 days before the infection. The cytotoxic T cell activity was either not influenced or significantly modified (p less than 0.05), i.e. increased or decreased as compared to the control, depending on the dose and timing of thymopentin. A correlation between increased cytotoxic T cell activity and protection against mortality can be demonstrated, while no protection was observed in dose regimens where the cytotoxic T cell activity became reduced. The results are discussed in connection with earlier clinical studies in which the beneficial effect of thymopentin has been demonstrated in frequently relapsing herpes labialis and herpes genitalis patients.

Immune responses to DNA free herpes simplex proteins in man.

The data presented confirm in human volunteers our previous observations in animal models. The DNA free HSV 2 subunit vaccine used elicited an antibody and a cell-mediated immune response in 15 subjects without past evidence of HSV 1 or HSV 2 infections and increased the immunity level in 28 subjects suffering from HSV 1 or HSV 2 infections. Although we did not follow a double-blind, placebo controlled protocol our results suggest that the vaccine may reduce the frequency and severity of HSV infections. The time between the recurrences, the pain and the time to complete healing decreased significantly after the vaccination.

Immune response to a DNA free herpes simplex vaccine in man.

A DNA-free subunit herpes simplex virus (HSV) vaccine was administered to 15 volunteers without past evidence of HSV infection and to 25 patients with severe recurrent HSV infection. The immune response to the vaccine in these patients was compared to the immunological status of 20 non-vaccinated control patients with recurrent HSV infection. The vaccine elicited antibody and cell-mediated immunity (CMI) in the 15 subjects without past evidence of HSV infection and this response was similar to that observed after a natural infection. Among the 25 patients who were suffering from recurrent HSV infection the vaccine elicited complement dependent cytotoxic antibodies in 13 of these patients who did not possess these antibodies and increased significantly the titers of these antibodies in the 12 other patients. The vaccine gave a significant increase of the titers of the other specific antibodies as well as the level of cell-mediated immunity. The increase of the immunity level in these latter patient was not due to normal variations since in the non-vaccinated control group the antibody titers and CMI remained stable during the same period of time.

Efficacy of a nucleic acid free herpetic subunit vaccine.

The efficacy of immunization with an herpes simplex subunit vaccine, free of nucleic acid, was evaluated in mice, rabbits and monkeys. One injection of 3 micrograms per kg of body weight elicited both humoral and cell-mediated immunity in all the animals studied. Furthermore, the immunization reduced significantly the mortality to a subsequent challenge with live herpes simplex virus in mice and rabbits (p less than 0.01).

Antibody and cell-mediated immunity to a DNA free herpes simplex subunit vaccine.

The immunogenicity of a DNA free herpes simplex subunit vaccine was evaluated in chimpanzees and rabbits. The results clearly demonstrate that 1 injection of 3 micrograms/kg elicited antibodies as well as cell-mediated immunity in all the animals studied. These antibodies persisted for at least 6 months. Furthermore the vaccine also protected 50% of the animals against an experimental infection and reduced the rate of latent infection in nervous sensory ganglia.

Diagnosis of hepatitis B by Dane particle associated DNA polymerase assay.

We have studied prospectively 478 subjects exposed to hepatitis B virus and 20 pregnant women who developed HBs antigen during the last trimester of pregnancy. The results suggest that the DNA polymerase assay might be useful for the diagnosis of hepatitis B infection and that in confirmed cases of hepatitis, the enzyme might be detected in the absence of HBs antigen. HBe antigen appeared in 19% of those subjects who developed HBs and a positive correlation between HBe antigen and DNA polymerase was found in 40% of the cases positive for this antigen. The data presented also suggest that HBe antigenemia in pregnant women is not consistently associated with HBs infection in the babies born to them. However the children born to HBe positive mothers are at higher risk than those born to HBe negative mothers.

Rapid detection of IgG and IgM antibodies for cytomegalovirus by the enzyme linked immunosorbent assay (ELISA).

A simple solid phase enzyme immunoassay for the detection of immunoglobulin G and M to cytomegalovirus (CMV) is described. Using this test IgM antibodies to CMV were detected in 0.7 per cent of newborns and regularly after CMV infection in transplant patients, furthermore in these latter patients IgM production was prolonged for several months. For the determination of IgG the enzyme immunoassay was more sensitive than the complement fixation test (CF) and the antibody titres were 4 to 8 fold higher. Since the ELISA test is rapid, specific and unexpensive it can become an acceptable routine diagnostic procedure.

Early diagnosis of Hepatitis B by Dane particle associated DNA polymerase assay.

We have studied prospectively 178 subjects exposed to hepatitis B and 120 haemodialysed patients for the presence of HGs antigen, e antigen and DNA polymerase as well as for anti-HBs and anti-HBc antibodies. The results suggest that the DNA polymerase assay enables us to diagnose hepatitis B earlier than the radioimmunoassay for HGs and that DNA polymerase might be present in the blood in the absence of HBs in cases of confirmed hepatitis B. A posititive correlation between e antigen and DNA polymerase was observed in 83% of the patients on haemodialysis who developed hepatitis B but only in 9% of normal patients developing the same disease.

Efficacy and immune response to rubella subunits vaccines.

Antibody and cell-mediated immunity (CMI) was measured in rabbits immunized with wild or attenuated virus and in rabbits vaccinated with a rubella subunit vaccine containing the viral envelope or nucleocapsid. The data presented show that a subunit vaccine containing the envelope proteins could induce a good antibody and CMI response. The results also suggest that such a vaccine was highly effective since 60 per cent of the rabbits immunized with the envelope proteins were protected when challenged with wild virus. This protection rate was identical as the protection achieved with a live attenuated vaccine.