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M Cranage

Publications and source records attributed to M Cranage.

27 records · Page 2Linked to original sources
PubMed1994

Antibodies to human and non-human primate cellular and culture medium components in macaques vaccinated with the simian immunodeficiency virus.

Inactivated simian immunodeficiency virus (SIV) grown in a human T-cell line induces protection from infection by the virus in macaques. However, observations that immunization with uninfected human T cells or with SIV-1 prepared in human T cells can also induce protection, has raised the possibility that protective antigens could be of human cellular origin. Sera from animals immunized with fixed infected and uninfected human T cells, as well as from animals immunized with partially purified cell-free SIV have been examined for their ability to bind to human and macaque peripheral blood mononuclear cells (PBMC) and to-components present in fetal calf serum (FCS) in which the cells were grown. Analysis by flow cytometry suggests that antibodies to human cell surface antigens can be elicited with both inactivated SIV grown in human T cells and by uninfected T cells. There was a significant association between the presence of anti-cell antibodies and protection from infection. However, anti-cell surface antibodies were not detected with macaque mononuclear cells by flow cytometry or by immunoprecipitation, unless these cells were first treated with FCS or activated by a mitogen. Immunoprecipitation of resting human PBMC with sera from immunized animals suggests the presence of antibodies to class I heavy and light chains [beta 2-microglobulin (beta 2 m)] and to bovine beta 2m, which may originate in FCS used to grow the cell line. Antibodies to CD4 were also found in sera from animals immunized with SIV grown in human T cells. We suggest that human cellular components augmented by FCS elicit anti-class I heavy chain, beta 2m, CD4 and FCS antibodies which may be responsible for protection against SIV infection in macaques.

Animals↗
PubMed1992

Population sequence analysis of a simian immunodeficiency virus (32H reisolate of SIVmac251): a virus stock used for international vaccine studies.

The virus structural genes gag and env (both gp120 and gp41 regions) of the 32H isolate of SIVmac251 were amplified using the polymerase chain reaction (PCR). The proviral template used in the PCR was DNA isolated from cells used to prepare several experimental SIV vaccines, which have been tested in simians, and a standard challenge stock of virus, which has been used in international collaborative studies. The PCR products were cloned and the nucleotide sequences of several clones were determined for each gene. From a comparison of the sequences obtained the predominant amino acid sequences of gag and env were predicted and the degree of sequence heterogeneity was determined. Conserved and more variable regions of each protein were identified. The gp120 region of env was more heterogeneous than gag or the transmembrane protein of env (gp41). Within gp120, sequence variability was concentrated to specific regions equivalent to the V1, V2, and, to a lesser extent, the C1 regions identified for human immunodeficiency virus type 1 (HIV-1). In contrast the region equivalent to the hypervariable "V3-loop" of HIV-1 was highly conserved. The implications of the data is discussed in relation to the ability of this virus stock to prepare effective vaccines against SIV.

Amino Acid Sequence↗
PubMed1990

The use of the polymerase chain reaction for the detection of Simian immunodeficiency virus in experimentally infected macaques.

A rapid, non-radioactive assay for the detection of proviral Simian immunodeficiency virus (SIV) in tissue-culture cells is described. The assay is based on the co-amplification of the SIV env and gag genes by the polymerase chain reaction (PCR). When the gag PCR product is blotted onto a nylon membrane and hybridised to a radioactive oligonucleotide probe, the assay can also be used to detect the SIV gag gene in DNA isolated directly from experimentally infected cynomolgus macaque lymphocytes. This provides a valuable assay for the presence of proviral SIV during animal trials of AIDS vaccines and chemotherapeutics.

Animals↗
PubMed1990

Induction of immunoglobulin G Fc receptors by recombinant vaccinia viruses expressing glycoproteins E and I of herpes simplex virus type 1.

Glycoprotein E (gE) of herpes simplex virus type 1 (HSV-1) will bind immunoglobulin G (IgG) (Fc) affinity columns (R. B. Bauke and P. G. Spear, J. Virol. 32:779-789, 1979), but recent evidence suggests that the HSV-1 Fc receptor is composed of a complex of gE and glycoprotein I (gI) and that both gI and gE are required for Fc receptor activity (D. C. Johnson and V. Feenstra, J. Virol. 61:2208-2216, 1987; D. C. Johnson, M. C. Frame, M. W. Ligas, A. M. Cross, and N. D. Stow, J. Virol. 62:1347-1354, 1988). We have expressed gE and gI, either alone or in combination, on the surface of HeLa cells by using recombinant vaccinia viruses and have measured Fc receptor activity by Fc-rosetting or IgG-binding assays. Expression of gE alone resulted in the induction of Fc receptor activity, while expression of gI alone gave no detectable Fc binding. Coexpression of gE and gI resulted in higher levels of IgG binding than did expression of gE alone, despite the fact that under conditions of coexpression, the levels of surface gE were reduced. We propose that gE and gI together form a receptor of higher affinity than gE alone and that HSV-1 therefore has the potential to induce two Fc receptors of different affinities.

Animals↗
PubMedDate not supplied

Preliminary report: protection of cynomolgus macaques against simian immunodeficiency virus by fixed infected-cell vaccine.

Cynomolgus macaques were vaccinated with inactivated simian immunodeficiency virus-infected cells and 'Quil-A' as adjuvant at 0, 4, 8, and 36 weeks or at 0, 4, 8, and 16 weeks. 2 weeks later these animals, together with a similar unvaccinated group, were challenged with 10 MID50 (50% monkey infectious doses) of a pool of SIVmac251 previously titrated in vivo. Virus was repeatedly isolated from unvaccinated animals on at least five separate occasions and proviral DNA was detected in circulating lymphocytes by polymerase chain reaction amplification. By contrast, virus and proviral DNA were not found in any of the vaccinated animals. However, the same vaccination regimen used after live virus challenge did not eliminate virus from previously infected macaques.

Adjuvants, Immunologic↗
PubMedDate not supplied

Mechanisms of protection induced by attenuated simian immunodeficiency virus. IV. Protection against challenge with virus grown in autologous simian cells.

Attenuated simian immunodeficiency virus (SIV) induces potent protection against infection with wild-type virus, but the mechanism of this immunity remains obscure. Allogeneic antibodies, which arise within animals as a result of SIV infection, might protect against challenge with exogenous SIV grown in allogeneic cells. To test this hypothesis, eight macaques were infected with attenuated SIV and subsequently challenged with wild-type SIV grown in autologous cells or heterologous cells. The results clearly demonstrated that animals infected with attenuated SIV are protected against wild-type SIV grown in autologous or heterologous cells. Thus, the hypothesis that live attenuated SIV protects by the induction of allogeneic antibodies is not tenable.

AIDS Vaccines↗
PubMedDate not supplied

A formalin inactivated whole SIVmac vaccine in Ribi adjuvant protects against homologous and heterologous SIV challenge.

Eight monkeys were immunized at 0, 4, 9, and 18 weeks with a total of 2 mg of formalin inactivated SIVmac vaccine with Ribi adjuvant. Two weeks after the last booster four immunized monkeys and two controls were challenged with 10 MID50 of live homologous virus SIVmac, and the remaining four vaccinated animals along with two controls were challenged with the heterologous SIVsm strain. All eight vaccinated monkeys resisted the virus challenge, whereas all controls became infected. Three months after the first challenge the monkeys were rechallenged with the same virus strain, without further boosting. Two of four vaccinated monkeys were still resistant to the homologous SIV strain, and three of four monkeys were resistant to the heterologous SIVsm strain. This study demonstrates vaccine induced cross-protection between SIV strains.

Adjuvants, Immunologic↗
PubMedDate not supplied

Whole inactivated SIV vaccine grown on human cells fails to protect against homologous SIV grown on simian cells.

Several groups have reported protection against experimental SIV infection in macaques immunized with a whole inactivated virus vaccine. The aim of the current study was to investigate whether five macaques vaccinated with whole inactivated SIV and previously shown to be protected against challenge with two divergent strains of SIV grown on human cells could resist challenge with a subsequent homologous SIV grown on macaque cells. We show here that this same vaccine did not protect when the challenge virus was grown on primary cells of monkey origin.

AIDS Vaccines↗