Live Varicella Vaccine Research Articles

Long-Term Protective Immunity of Recipients of the OKA Strain of Live Varicella Vaccine

In spite of close contacts with patients who had varicella, 101 of 106 (95%) healthy and sick children (142 of 147 (97%) exposures of these children) who had received the OKA strain of live varicella vaccine 7 to 10 years earlier were protected against the disease completely. Among them, 37 of 38 (97%) vaccine recipients who received immunologic testing had varicella-zoster virus (VZV) antibodies tested by fluorescent antibody to membrane antigen method with a geometric mean titer of 1:9.3, and 37 of the 38 (97%) showed positive skin reaction to varicella-zoster virus antigen with erythema (mean diameter 13.4 mm). These findings were compared with those for 29 children who had contracted typical varicella 7 to 10 years earlier, whose seropositive rate was 100% with a geometric mean titer of 1:10.5, and 97% of whom (28/29) had positive skin reaction with mean diameter of 12.9 mm. These results indicate that the vaccine-induced protective immunity persists for approximately one decade and is almost equal to the long-term immunity following natural infection.

Seroepidemiologic behavior of varicella zoster virus infection in a semiclosed community after introduction of VZV vaccine

A survey of varicella and measles has been made in a semiclosed institution housing infants and children in Osaka since 1950. Live measles and varicella vaccines were introduced into the institution in 1974 and 1975, respectively. Nine of 10 measles outbreaks occurred during the 24 years before use of measles vaccine, and only one occurred during the 9 years after introduction of measles vaccine. In contrast, the incidence of varicella outbreaks has not been reduced after introduction of varicella vaccine, although the rate of immune individuals in the population against varicella has been kept at 74.2% for the 8 years since 1975, which was higher than that against measles (65.8%) during the same period. All successfully vaccinated children, however, were resistant to clinical varicella, and the number of clinical cases has been markedly reduced. Using the fluorescent antibody to membrane antigen and varicella zoster virus skin testing, the kinetics of secretory, humoral, and cellular immune responses to VZV was examined in vaccinated and naturally infected subjects and found to be comparable in both groups during repeated exposure to varicella epidemics. These results suggest that the seroepidemiologic behavior of varicella would not be significantly altered after introduction of varicella vaccine, in contrast to that of measles since general use of measles vaccine.

Biologic and biophysical markers of a live varicella vaccine strain (Oka): identification of clinical isolates from vaccine recipients.

Possible biologic and biophysical markers of the Oka vaccine strain of varicella-zoster virus (VZV) were explored. The ratio between the infectivity of the vaccine strain in guinea-pig embryo fibroblasts and that in human embryo fibroblasts was consistently higher than the corresponding ratios for wild-type strains; this result seemed to correlate with the passage history of the vaccine strain in guinea-pig embryo fibroblasts. According to profiles of cleavage of digested DNA by various restriction endonucleases, the mobility of one fragment (K) produced by restriction endonuclease Hpa I was unique to the Oka strain. Nine clinical isolates from vaccine recipients (seven with varicella and two with zoster) were examined by both methods (infectivity and cleavage profiles) to determine whether or not these strains were vaccine derived. The laboratory judgments obtained by the two methods were in agreement and were consistent with clinical conclusions concerning five of the strains. Since the test of relative infectivity is simple and convenient, it is suitable for differentiation of the vaccine strain from other wild-type strains; if the results are not conclusive, profiles of cleavage by Hpa I may be helpful in reaching a definite judgment.

Five-Year Follow-up Study of Recipients of Live Varicella Vaccine Using Enhanced Neutralization and Fluorescent Antibody Membrane Antigen Assays

Twenty-six healthy children susceptible to varicella were inoculated with the OKA strain of live attenuated varicella vaccine. All of the recipients showed good antibody responses without adverse clinical reactions. The seropositivity rate 5 years after vaccination was 100% by the enhanced neutralization test and 96% by the fluorescent antibody membrane antigen (FAMA) test. None of the recipients contracted varicella in spite of documented contact exposure. None of the children developed herpes zoster during the 5-year observation period. The results suggest that attenuated varicella vaccine has long-term protective efficacy.

ADMINISTRATION OF LIVE VARICELLA VACCINE TO CHILDREN WITH LEUKAEMIA

Live varicella vaccine was given to twenty-three children with lymphoreticular malignancies, twelve whose chemotherapy was complete and eleven who were still receiving therapy. Seroconversion was observed in all twenty-three children, only one of whom lost his vaccine-induced antibody. Eight of the children experienced thirteen exposures to varicella, including four continuing exposures in their households. Varicella, manifested by the appearance of seven vesicular lesions, developed in only one. In all but two of the children an in-vitro blastogenic response to varicella/zoster-virus (VZV) antigen developed; both children had a biphasic rash after immunisation. A sibling of one of these children seroconverted without clinical evidence of varicella, presumably because of infection with vaccine virus. None of the other household contacts had significant rises in VZV antibody. VZV was not isolated from the blood, throat, or urine samples of the twenty-three vaccinees tested.

Application of a Live Varicella Vaccine to the Immunosuppressive Children and the Incibence of a Case of Herpes Zoster after Vaccination

AbstractA live varicella vaccine was applied to 13 susceptible children to varicella virus. Three were receiving steroid therapy, and one of them was treated with both steroid and anticancer drugs. Immunosuppressive therapy and anticancer medication were not suspended before and after vaccination. Serological responses were observed in 11 of 13 vaccinated children by fluorescent antibody to membrane antigen (FAMA) test 6 to 7 weeks after Vaccination. Mild rash appeared as only a clinical reaction in 3 of the vaccinated children. However, 3 and a half months later, a vaccinee with acute myeloblastic leukemia, developed herpes zoster. Our observation suggested a possibility of contracting zoster in immune compromised hosts after vaccination with a live varicella vaccine.

Application of Live Varicella Vaccine to Children with Acute Leukemia or Other Malignancies Without Suspension of Anticancer Therapy

A live varicella vaccine was given to children with acute leukemia or other malignancies with minimal clinical reactions.1 In that study, anticancer medication was suspended beginning one week before vaccination and was not resumed until one week after vaccination. In the present study, we attempted to vaccinate such children without suspension of anticancer medication. SUBJECTS AND METHODS Fifteen children with acute leukemia, 12 children with malignant solid tumors (4 neuroblastoma, 4 retinoblastoma, 2 Wilms tumor, 2 teratocarcinoma), and 1 child with lymphosarcoma received a live varicella vaccine1 (500 plaque forming unit/dose) without suspension of anticancer medication. All of these children had been in remission.

Use of live varicella vaccine in childen with acute leukemia.

Seven children with acute leukemia were given a live attenuated varicella vaccine and successfully seroconverted with minimal clinical reactions. One of them was vaccinated immediately after the contact with natural varicella and successfully prevented from natural infection.

Clinical and Serologic Testing of a Live Varicella Vaccine and Two-Year Follow-up for Immunity of the Vaccinated Children

A live varicella vaccine derived from the Oka strain was given on 181 children who had no history of varicella and were seronegative by complement fixation (CF) and neutralization (NT) tests; 125 children were hospitalized and 54 were receiving steroid therapy. Overall, seroconversion was achieved in 85.1% of the children by the CF test and in 97.8% by the NT test. Clinical reaction consisting of mild fever and rash appeared in only two children. One hundred seventy-nine of the vaccinated children were followed up by questionnaire and 51 were followed up serologically approximately two years later, at which time 10 of 51 (19.6%) were seropositive by the CF test and 50 of 51 (98.0%) by the NT test. Only one out of 80 children who had postvaccinal contact with varicella contracted mild varicella 16 months after vaccination. None of the vaccinees developed herpes zoster. These results suggest that this live varicella vaccine may safely and effectively be used for children with or without underlying diseases, including those receiving steroid therapy, and that immunity of at least two years' duration is conferred upon the vaccinated subjects.

Application of a Live Varicella Vaccine in Children With Acute Leukemia or Other Malignant Diseases

A live varicella vaccine was used in 11 susceptible children in remission from acute leukemia, ten of whom had been in remission for six months or less, and in 6 children with neuroblastoma and retinoblastoma. In the immunological checkup before vaccination, most of them showed a positive reaction in the skin tests with dinitrochlorobenzene, phytohemagglutinin, purified protein derivative, and viral antigens. Leukopenia (three cases, less than 3,000/cu mm) and decreased IgG level (two cases, 380 mg/dl and 445 mg/dl) were observed in the children with leukemia. Anticancer medication was suspended from one week before vaccination to one week after vaccination. The only clinical reaction was a minute rash that appeared three weeks after vaccination in two children with leukemia and that disappeared within three days. Serological responses by complement fixing and neutralizing (NT) tests were detected in all the vaccinated children four weeks after vaccination, and NT antibody was still detected 28 months after vaccination in the two patients tested. Three of the vaccines were exposed to natural varicella at home and in the classroom 2 to 18 months after vaccination, but they were free from any varicella symptoms.

LIVE VACCINE USED TO PREVENT THE SPREAD OF VARICELLA IN CHILDREN IN HOSPITAL

A strain (Oka strain) of varicella virus was attenuated by cultivating it serially in human embryonic lung cells and then in guineapig embryo (G.P.E.) cells. Subcutaneous injection of the virus stimulated the production of complement-fixing (C.F.) antibody without clinical reactions in normal susceptible children. The virus propagated in human diploid (WI-38) cells after passage in G.P.E. cells was also effective in inducing an immunological response without clinical reactions in normal susceptible children. The attenuated virus derived from G.P.E. cells was used in 23 children in hospital with no history of varicella and no detectable C.F. antibody immediately after symptoms of varicella were found in a patient in the children's ward. There was an antibody response in all the vaccinated children including those who were receiving steroid therapy. No troublesome clinical reactions were noticed and the spread of varicella infection was prevented, with the exception of one severe case in an unvaccinated patient. 16 children with nephritis and nephrotic syndrome were also vaccinated. An immunological response was observed in all the vaccinated children, with no clinical reactions and no abnormal laboratory findings when blood and urine samples were examined. These results suggest that it is possible to prepare a live varicella vaccine which may be safely and effectively used for high-risk children as well as normal children.

Localization of varicella virus in tissue culture

This chapter discusses the clinical and serological aspects of varicella-zoster virus (VZV) infection. From the immunological point of view, VZV is a particularly interesting virus as it causes two very apparent entities—chickenpox and zoster—to which latency of VZV is closely associated. For recovery and protection against the disease and reactivation of VZV, the role of cell-mediated immunity has been recognized and the VZV skin-test antigen recently developed will be of much use experimentally and clinically because of its technical convenience and excellent sensitivity. Studies on virus proteins, particularly on virus glycoproteins with regard to the humoral and cell-mediated immunity of this virus, are promoted with the development of monoclonal antibodies. Progress has been notable in the prevention and treatment of chickenpox and zoster and in the development of a live varicella vaccine. Clinical studies on live varicella vaccine have been helping to elucidate the immune mechanisms involved in VZV infection. Control of chickenpox will be possible, at least in high-risk children, in the near future.