Biomedical subjects

B J Neff

Publications and source records attributed to B J Neff.

14 recordsLinked to original sources

PubMed1991

Oka/Merck varicella vaccine in healthy children: final report of a 2-year efficacy study and 7-year follow-up studies.

A large double-blind, randomized, placebo-controlled trial of live attenuated Oka/Merck varicella vaccine was conducted among healthy children, 1-14 years of age. During the first varicella season, the efficacy of the vaccine among susceptible children was 100%1. During the second varicella season, 22 children were diagnosed with varicella; 21 cases in placebo recipients and one in a vaccine recipient. The overall efficacy of the vaccine through two varicella seasons was 98%. After the code for the study was broken, the original group of vaccine recipients continued to be followed for development of varicella. The estimated proportion of vaccine recipients who remained varicella-free at the end of 7 years was 95%. The 23 cases of varicella that occurred in vaccine recipients over the 7-year period were considerably milder than natural varicella. The average number of lesions was 53, 50% of the children had non-vesicular rashes, and 14% of the children had a temperature greater than or equal to 38.9 degrees C (102 degrees F), oral. The persistence of antibody in a subset of vaccine recipients followed for 6 years was 100%.

Adolescent↗

PubMed1986

Purification of individual varicella-zoster virus (VZV) glycoproteins gpI, gpII, and gpIII and their use in ELISA for detection of VZV glycoprotein-specific antibodies.

We have utilized monoclonal antibodies in immune affinity chromatography to purify each of the 3 major glycoproteins of varicella-zoster virus (VZV), gpI, gpII, and gpIII, in immunologically active form. Upon injection into guinea pigs, each preparation elicited the production of specific antibodies capable of immunoprecipitating the homologous glycoprotein and of neutralizing VZV infectivity in vitro. Also, total glycoproteins from VZV-infected cells have been purified by lectin affinity chromatography. Each of the individual purified glycoproteins, as well as total VZV glycoproteins and appropriate uninfected cell protein controls, have been employed as solid-phase reagents in enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies directed against specific VZV glycoproteins. The specificity of the purified glycoproteins as ELISA reagents was verified by the ability of individual monoclonal antibodies to bind specifically to individual glycoprotein preparations. We have demonstrated the utility of the glycoprotein-specific ELISA by detecting antibodies in sera from post-zoster and post-varicella patients. The assay detects antibodies directed against each of the 3 major glycoproteins and is sensitive enough to detect antibodies in a 1:320 000 dilution of some sera. This assay, as well as the purified individual glycoproteins per se, should prove to be very useful reagents in understanding the role of each of gpI, gpII, and gpIII in immunity to VZV.

Animals↗

PubMed1985

Live Oka/Merck varicella vaccine in healthy children. Further clinical and laboratory assessment.

A clinical trial among 137 healthy children, ages 1 to 12 years, was conducted with four different doses (4,350, 870, 435, and 43 plaque-forming units [pfu]) of live Oka/Merck varicella vaccine to evaluate clinical reactions and selected laboratory parameters and to determine the minimum effective dose and induction time of antibody. The vaccine was well tolerated with no significant difference in the rate of reported symptoms by dose. The frequency of varicellalike rash was 3% (4/137); all rashes were mild. Serum aminotransferase values were essentially unchanged after vaccination. Minor variations found in platelet counts after vaccination were not associated with any bleeding, bruising, or clotting. Among initially seronegative children who received doses of 435 pfu or greater, 94% assayed at two weeks and 100% assayed at four or six weeks seroconverted. The geometric mean titers were similar for all four doses at six weeks. IgG and IgA responses were demonstrated with no relation to the vaccine dose.

Alanine Transaminase↗

PubMed1984

Live attenuated varicella virus vaccine. Efficacy trial in healthy children.

We conducted a double-blind, placebo-controlled efficacy trial of the live attenuated Oka/Merck varicella vaccine among 956 children between the ages of 1 and 14 years, with a negative clinical history of varicella. Of the 914 children who were serologically confirmed to be susceptible to varicella, 468 received vaccine and 446 received placebo. The vaccine produced few clinical reactions and was well tolerated. There was no clinical evidence of viral spread from vaccinated children to sibling controls. Approximately eight weeks after vaccination, 94 per cent of the initially seronegative children who received vaccine had detectable antibody to varicella. During the nine-month surveillance period, 39 clinically diagnosed cases of varicella, 38 of which were confirmed by laboratory tests, occurred among study participants. All 39 cases occurred in placebo recipients; no child who received vaccine contracted varicella. The vaccine was 100 per cent efficacious in preventing varicella in this population of healthy children (P less than 10(-9).

Adolescent↗

PubMed1984

Immunogenicity of wild and attenuated varicella-zoster virus strains in rhesus monkeys.

Thirty susceptible rhesus monkeys were inoculated with cell-free varicella-zoster virus strain OKA or strain KMcC. Both wild and attenuated strains were used. No clinical signs characteristic of human varicella were seen in any of the animals. Virus was not isolated from throat swabs, blood, or cerebrospinal fluid. Antibodies were measured by an enhanced plaque neutralization test. The wild and attenuated OKA strains produced comparable levels of antibodies for 3 months after inoculation. Attenuated KMcC strains produced lower titers than the wild strain. On rechallenge 3 months after primary inoculation animals boostered with the attenuated OKA strain developed significantly higher antibody titers than animals receiving the wild strain. Animals primed and challenged with the attenuated KMcC strains showed significantly lower antibody titers than animals which received the wild strain. The results indicate that the immunogenicity of attenuated OKA and KMcC strains in rhesus monkeys parallels the experience obtained with these strains in humans.

Animals↗

PubMed1984

Three major glycoprotein genes of varicella-zoster virus whose products have neutralization epitopes.

Varicella-zoster virus (VZV) codes for approximately eight glycosylated polypeptides in infected cell cultures and in virions. To determine the number of serologically distinct glycoprotein gene products encoded by VZV, we have developed murine monoclonal antibodies to purified virions. Of 10 monoclonal antibodies which can immunoprecipitate intracellular VZV antigens and virion glycoproteins, 1 (termed gA) reacted with gp105, 1 (termed gB) reacted with gp115 (intracellular only), gp62, and gp57, and 8 (termed gC) reacted with gp92, gp83, gp52, and gp45. The anti-gA monoclonal antibody neutralized VZV infectivity in the absence of complement. All eight anti-gC monoclonal antibodies neutralized only in the presence of complement. An anti-gB monoclonal antibody obtained from another laboratory also neutralizes in the absence of complement. Since the above reactivities account for all major detectable VZV glycoprotein species, the data strongly suggest that VZV has three major glycoprotein genes which encode glycosylated polypeptides with neutralization epitopes.

Animals↗

PubMed1983

Live attenuated varicella vaccine: the KMcC strain in healthy children.

The KMcC strain of live, attenuated varicella-zoster virus vaccine was studied in healthy children as a preliminary step toward varicella vaccine studies with this strain in children with leukemia. Forty-three children were immunized: 26 with the 40th passage vaccine and 17 with the 50th passage. Studies included surveillance for clinical reactivity, oropharyngeal excretion of vaccine virus, viruria, and viremia. Antibody responses were assayed by fluorescent antibody to membrane antigens and immune adherence hemagglutination. Cell-mediated immune responses were assayed by lymphocyte proliferation to varicella-zoster virus specific antigens. There was 100% seroconversion to the KMcC passage 40 and 50 vaccines (by fluorescent antibody to membrane antigen assay). Every child studied developed in vitro lymphocyte proliferation to varicella-zoster virus antigens. Papular skin lesions, probably vaccine related, occurred in 31% of the 40th passage vaccinees but in only 6% of the 50th passage vaccinees. The 50th passage KMcC strain vaccine is sufficiently immunogenic and safe to initiate clinical studies with leukemia patients.

Adolescent↗

PubMed1981

Restriction endonuclease analysis of the DNA from varicella-zoster virus: stability of the DNA after passage in vitro.

DNA was extracted from nucleocapsids isolated from WI-38 cells infected with two different strains of varicella-zoster virus (VZV). The DNAs were treated with each of six restriction endonucleases (EcoRI, HindIII, Bg/I, Bg/II, Sal I and Bam-HI) and small, but reproducible differences in restriction endonuclease patterns were observed. These strains were passaged in WI-38 cells and in primary guinea-pig embryo (GPE) cells, followed by restriction endonuclease analysis of the DNAs. No changes were observed in the restriction prpofile of the DNA of one of the strains (VZV-KMcC) after 46 passages in WI-38 cells but small differences were observed after 72 passages. No changes were observed after 30 passages of another strain (VZV-AW) in WI-38 cells. Twenty passages of VZB-KMcC in GPE cells did result in minor alterations of its DNA. It was concluded that VZV DNA was sufficiently stable after multiple passages in WI-38 cells to make restriction endonuclease analysis a valuable epidemiological tool for strain differentiation.

Animals↗

PubMed1981

Immune response after exposure to varicella zoster virus: characterization of virus-specific antibodies and their corresponding antigens.

Fourteen varicella zoster virus antigens were identified that induce antibodies during primary and recurrent infections. These antigens, which included the major nucleocapsid polypeptide (molecular weight, 155,000) and three glycoproteins (molecular weights, 130,000, 88,000, and 60,000, respectively) plus a number of minor antigens, were identified in radioimmunoprecipitation assays, using [35S]methionine-labeled extracts of cells infected with varicella zoster virus and sera from patients with primary and recurrent viral infections. No significant and reproducible differences were observed between early convalescent sera from cases with natural chicken pox and sera from cases with zoster in their ability react with viral antigens. Sera that were taken many years after episodes of chicken pox still retained their ability to react with the major viral antigens.

Antibodies, Viral↗

PubMed1981