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Biomedical subjects

G C Schild

Publications and source records attributed to G C Schild.

At least 19 recordsLinked to original sources
PubMed1991

Studies on the immunogenicity of Chinese hamster ovary cell-derived recombinant gp120 (HIV-1IIIB).

Recombinant DNA-derived gp120 (HIV-1IIIB) expressed in chinese hamster ovary cells elicited specific humoral and cell-mediated immune responses in a variety of mammals. Antisera from immunized rabbits, sheep and goats recognized virus-derived gp120 and its precursor (gp160). Neutralizing antibodies were also elicited, but only in a few animals, and this may be related to the protein's susceptibility to cleavage through the neutralizing domain. However, in rabbits the degree of cleavage of gp120 had little or no effect on its antigenicity or immunogenicity. All antisera had limited cross-reactivity to envelope glycoproteins from a panel of HIV-1 isolates suggesting that immunodominant antibody epitopes are in variable regions of the recombinant gp120. Antigen-specific T-cell responses were detected in immunized macaques and were found to be stronger and more prolonged when gp120 was administered in Freund's adjuvant rather than alum.

Animals↗
PubMed1991

Direct isolation in eggs of influenza A (H1N1) and B viruses with haemagglutinins of different antigenic and amino acid composition.

Influenza A (H1N1) and influenza B viruses from clinical samples were isolated in the amniotic cavity of embryonated hens' eggs by classical techniques and propagated in the allantoic cavity. Virus progeny from different eggs which had been inoculated with virus material from the same clinical sample possessed antigenically distinguishable haemagglutinins (HAs). Virus progeny of some eggs possessed HAs which were serologically identical to those of virus isolated in parallel in mammalian (MDCK) cells. These egg-grown viruses possessing HAs with the antigenic phenotype of mammalian cell-grown viruses appeared to be antigenically related to epidemic influenza virus because post-infection human sera reacted to high titre with the virus HA. Specific nucleotide changes were detected in the HAs of the viruses isolated directly in eggs at positions 163 and 189 for influenza A (H1N1) viruses or positions 141 and 196 to 198 for influenza B viruses. Egg-isolated viruses which possessed the antigenic phenotype of mammalian cell-grown viruses retained glycosylation sites at positions 163 and 196. The viruses isolated directly in embryonated hens' eggs which possessed the HA antigenic phenotype and glycosylation sites of MDCK cell-grown virus can, unlike the latter viruses themselves, be used as candidate influenza vaccine viruses.

Amino Acid Sequence↗
PubMed1990

A host-cell-selected variant of influenza B virus with a single nucleotide substitution in HA affecting a potential glycosylation site was attenuated in virulence for volunteers.

An influenza B virus was passaged in man (virus A) and then in human embryo trachea (C) and into embryonated eggs (D) or directly into eggs (B). Virus A, B, and C had the same (cell-like) haemagglutinin phenotype on reaction with selected monoclonal antibodies while D had an "egg-like" phenotype. The viruses were administered at a dose of 1,000 TCD50 (for MDCK cells) by intranasal inoculation to groups of 27 or 28 volunteers. Viruses A, B, and C all produced disease in six to eight volunteers, whereas D produced no illness and only four volunteers were infected. The viruses shed by the volunteers were indistinguishable from those with which they were inoculated. The haemagglutinin genes of the viruses were sequenced and changes were detected indicating amino acid substitutions at position 196-198 in the attenuated egg-grown virus D whereby a potential glycosylation site present in the other viruses was lost.

Amino Acid Sequence↗
PubMed1989

A collaborative study to establish the International Reference Reagent for hepatitis B vaccine containing plasma-derived hepatitis B surface antigen.

A collaborative study was conducted to establish a suitable international reference reagent for hepatitis B vaccine for use in immunogenicity assays. The limiting dilution required to induce antibodies in 50% of the test animals was determined for the proposed international reference reagent and three other plasma-derived hepatitis B vaccines. The minimum antigenic dose of these preparations varied widely (100-fold range) between laboratories. However, the expression of potencies of vaccines relative to the proposed International Reference Reagent reduced the variation between laboratories to within a 10-fold range. The reference reagent is intended for use in assays of hepatitis B vaccines in mouse (or guinea-pig) immunogenicity studies. For products made by different procedures, clinical trials in humans are necessary to establish a correlation between the immunogenic potency in animals and man.

Drug Stability↗
PubMed1989

Genetic basis of attenuation of the Sabin type 3 oral poliovirus vaccine.

The poliovirus type 3 Sabin oral poliovirus vaccine strain P3/Leon/12a1b differs in nucleotide sequence from its neurovirulent progenitor P3/Leon/37 by just 10 point mutations. The contribution of each mutation to the attenuation phenotype of the vaccine strain was determined by the construction of a series of recombinant viruses from infectious cDNA clones. The neurovirulence testing of recombinant viruses indicated that the attenuation phenotype is determined by just two point mutations: a C to U in the noncoding region at position 472 and a C to U at nucleotide 2034 which results in a serine-to-phenylalanine amino acid substitution in the structural protein VP3.

Amino Acid Sequence↗
PubMed1989

Medical Research Council AIDS Directed Program: program plan and research opportunities.

In 1987 the U.K. Medical Research Council established a Directed Programme of AIDS Research, the primary objective of which is the development of vaccines and therapeutic approaches against HIV infection and AIDS. The Programme's activities have been rapidly built up and by mid-1989 comprised some 130 individual research projects. The Programme provides the framework for a cohesive approach to AIDS research, comprising a clearly defined scientific development plan, the central provision of resources including laboratory reagents and specialized laboratory facilities and special arrangements for interaction with industry and for international collaboration and training. This article describes the organization, scientific strategies and progress of the Programme.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Protection against experimental infection with influenza virus A/equine/Miami/63 (H3N8) provided by inactivated whole virus vaccines containing homologous virus.

Thirty-one ponies immunized with inactivated virus vaccine containing A/equine/Miami/63 (H3N8) virus and six seronegative ponies were experimentally challenged with the homologous virus strain. All 6 unvaccinated ponies and 11 out of 31 vaccinated ponies became infected. A clear relationship between pre-challenge antibody, measured by single radial haemolysis (SRH), and protection was demonstrated as judged by virus excretion, febrile responses and antibody responses. Those ponies with SRH antibody levels greater than 74 mm2 were completely protected against challenge infection by the intranasal route.

Animals↗
PubMed1987

The receptor-binding and membrane-fusion properties of influenza virus variants selected using anti-haemagglutinin monoclonal antibodies.

A monoclonal antibody raised against X-31 influenza virus reacted with the majority of natural H3N2 viruses isolated between 1968 and 1982. A number of variants of X-31 and of a receptor-binding mutant of X-31 were selected by the antibody during virus replication in eggs and MDCK cells. Antibody-binding assays indicated that the viruses selected were not antigenic variants and analyses using derivatized erythrocytes showed that their receptor-binding properties differed from those of the parent viruses. The amino acid substitutions in the variants were all located in the vicinity of the receptor-binding site and the structural consequences are discussed in relation to the three-dimensional structure of X-31 HA. In addition all of the variants fused membranes at higher pH than wild-type virus indicating that structural modifications in the distal globular region of HA influence the low pH-induced conformational change required for membrane fusion.

Animals↗
PubMed1987

Structural changes in the haemagglutinin which accompany egg adaptation of an influenza A(H1N1) virus.

Antigenic changes are often induced in the haemagglutinin (HA) of human isolates of influenza A(H1N1) and B viruses during their isolation and propagation in embryonated hens' eggs. In this report we describe molecular changes in the HA of an A(H1N1) virus which accompany egg adaptation. The HA1 amino acid substitutions of egg-adapted variants are located in the vicinity of the receptor binding site. This suggests that egg-adapted variants are selected on the basis of altered receptor site specificity with concomitant effects on the antigenic configuration of the HA molecule. In this study, at least three antigenically distinct groups of egg-adapted variants were observed. These observations have implications for the indiscriminate use of egg-adapted viruses in sero-epidemiological studies and vaccine production.

Animals↗
PubMed1987

An improved immunoblotting procedure for the detection of antibodies against HIV.

Immunoblotting ('Western blotting') is routinely used for detection of antibodies against HIV in the diagnosis of HIV infection. We describe an improved procedure, which does not require virus purification and is easy to control for 'false-positive' results. The technique also does not produce erroneous results due to reactivity of the developing system with residual cellular proteins or viral antigens and does not give high nonspecific background staining. The technique can be applied to the detection of antibodies to HIV in serum, plasma, and blood products.

Acquired Immunodeficiency Syndrome↗
PubMed1987

Studies on the attenuation of the Sabin type 3 oral polio vaccine.

The genetic basis of attenuation of the poliovirus type 3 vaccine strain P3/Leon 12a1b has been investigated by comparing the nucleotide sequence of this strain with that of its neurovirulent progenitor P3/Leon/37 and by constructing recombinants between these two viruses using infectious cDNAs. Preliminary results suggest that attenuation is caused by just two point mutations, one occurring in the 5' non-coding region and the other causing an amino acid change in coat protein VP3.

Base Sequence↗