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Biomedical subjects

G L Ada

Publications and source records attributed to G L Ada.

At least 37 records · Page 2Linked to original sources
PubMed1988

Cellular immune responses in the murine lung to local immunization with influenza A virus glycoproteins in micelles and immunostimulatory complexes (iscoms).

Primary immunization with a single inoculum of either micelles or iscoms containing influenza A virus glycoproteins failed to induce either B or cytotoxic T (Tc) cell responses. In contrast, immunization with two inocula of iscoms, but not micelles, resulted in the appearance of influenza virus-specific antibody-secreting cells (ASC) but not Tc cells in the lung. There was a 10-fold increase in Tc cell precursor frequency and an increase in ASC generated by secondary in vitro stimulation of lung cell cultures obtained from mice primed with iscoms but not micelles. In mice primed with infectious virus, secondary immunization with either micelles or iscoms increased the number of ASC in the lung and elicited virus-specific Tc cell responses. In contrast homologous virus challenge failed to induce detectable secondary B or Tc cell responses.

Animals↗
PubMed1988

Modern approaches to vaccine development with special reference to the needs of developing countries.

Vaccination has proved to be one of the most effective public health measures to control infectious diseases. The eradication of smallpox by world-wide vaccination represents one of mankind's greatest achievements. Despite the availability of vaccines to control many diseases, they are generally under-used in many developing and some developed countries. However, there are many diseases for which current vaccines are inadequate or vaccines cannot be prepared using conventional approaches. This article describes the new approaches which are now available and are being used extensively to develop new vaccines against viral, bacterial and parasitic diseases. Success has already been achieved in a few cases and the prospect for others is encouraging. In addition, progress is being made to develop vaccines to control human fertility as this development is seen to complement the control of infectious diseases.

Developing Countries↗
PubMed1988

Prospects for HIV vaccines.

This article initially discusses the types of responses elicited by infectious agents, such as viruses and the role of each response in preventing, limiting, and clearing the infection. An important response is the generation of immunological memory, in both the B and T cell compartments. Generally, attenuated viral vaccines have been highly successful at inducing long-lived immunity but our understanding of the reasons for this comes from the study of model systems, such as murine influenza virus infections. Specific antibody may largely prevent infection and specific cytotoxic T cells and antibody-dependent cell cytotoxic reactions are the main mechanisms for clearing viral infections. Recent evidence shows that for some months after infection by HIV, a strong cytotoxic T (Tc) cell response occurs in infected, asymptomatic individuals; these cells are continuously generated by HIV-infected stimulator cells that most likely also serve as target cells in vivo. A low level of specific antibody is also formed and a number of reasons are listed to explain why HIV escapes antibody-mediated neutralization and infects cells expressing CD4 receptors. Cells of the macrophage/monocyte lineage are also infected and these express Fc and complement receptors; there is the strong possibility that infection of these cells occurred following the formation of complexes of infectious HIV with antibody to the surface antigen and attachment of complement components. The continuous presence of activated Tc cells that, in contrast to many other viral diseases, does not clear the infection strongly suggests that foci of infected cells sequestered from or resistant to immune control become established. These secrete virus that infects other (stimulator) cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1987

Persistence of influenza virus-specific antibody-secreting cells and B-cell memory after primary murine influenza virus infection.

Influenza virus-specific antibody-secreting cells (ASCs), enumerated using an ELISA-plaque assay, were found in the lung and spleen up to 18 months after primary murine influenza infection. The number of ASCs generated in stimulated lung and spleen cell cultures increased 50- to 200-fold after influenza infection. Whereas the level of response did not change in spleen cell cultures up to 18 months after infection, there was a gradual reduction in ASCs in lung cell cultures obtained more than 6 months after infection, predominantly due to a reduction in B memory cells. Homotypic re-infection increased ASCs in the lung only, whereas B-cell memory increased in both the lung and spleen. Although ASCs increased in both the lung and spleen after heterotypic challenge, ASCs and B-cell memory specific for the original subtype were not increased.

Animals↗
PubMed1987

Influenza-specific antibody-secreting cells and B cell memory in the murine lung after immunization with wild-type, cold-adapted variant and inactivated influenza viruses.

The development of regional B cell responses was studied in mice immunized intranasally with different influenza virus vaccines. The ca-variant virus was 100-fold less efficient than the parental virus in the induction of influenza virus-specific antibody secreting cells (ASCs) in the lung and failed to induce ASCs in the spleen. The ca-variant virus was also less efficient in priming for secondary IgG and IgA responses generated in vitro in both lung and spleen cell cultures. Protection against homotypic challenge in mice immunized by different vaccine strategies correlated with the development of pulmonary B cell responses rather than splenic responses. In particular, protection correlated with the presence of ASCs and IgG and IgA memory in the lung at the time of challenge.

Animals↗
PubMed1987

The roles of influenza virus haemagglutinin and nucleoprotein in protection: analysis using vaccinia virus recombinants.

Vaccinia virus recombinants expressing haemagglutinin (HA) or nucleoprotein (NP) from influenza virus A/PR/8/34 were used to investigate protective immunity in mice, with two protocols. Protection was assessed by mortality and morbidity rates and by lung virus titres after infection intranasally with A/PR/8/34. In the first protocol, mice immunized with vaccinia-HA recombinant virus and infected intranasally with A/PR/8/34 were almost totally protected, but mice immunized with vaccinia-NP virus were very poorly protected. In the second protocol, the recombinant viruses were used to stimulate in vitro T cells that are specific for HA and NP; both populations of T cells, when transferred to A/PR/8/34-infected mice, afforded good protection. The results indicate that an immune response specific for just HA provided protection that was almost indistinguishable from that provided by whole A/PR/8/34. On the other hand, immunization with vaccinia-NP provided poor protective immunity, despite the fact that transferred NP-specific T cells were very effective and vaccinia-NP immunization has previously been shown to stimulate cytotoxic T cells. These results demonstrate that a single viral antigen, delivered by live vaccinia virus, can provide effective protection, but that immunization for cross-protection against heterologous influenza virus remains elusive.

Animals↗
PubMed1986

Cell-mediated immune responses to influenza virus antigens expressed by vaccinia virus recombinants.

Recombinant vaccinia viruses enable studies of immune recognition of antigens expressed from single viral genes. We have constructed recombinants expressing the haemagglutinin (HA) and nucleoprotein (NP) genes of the influenza virus A/PR/8/34 (H1N1). These recombinant viruses together with a recombinant expressing the HA from influenza virus A/JAP/305/57 (H2N2) have been used to examine the cytotoxic T lymphocyte (CTL) response to these influenza virus antigens. Both antigens are recognised by murine CTL and recognition of HA is influenza virus subtype-specific, whereas recognition of NP is crossreactive. In limiting dilution studies approximately 10% of the influenza CTL response is HA-specific, while approximately 30% of the response is NP-specific. Despite the ability of NP to stimulate a significant CTL response, mice immunised with the NP-vaccinia recombinant are not as well protected from subsequent lethal challenge with influenza virus, as mice immunised with the HA vaccinia recombinant. These studies demonstrate that viral antigens expressed from vaccine recombinants can provide protective immunity and that the influenza-poxvirus recombinants can provide data on protective immunity generated by individual viral proteins.

Animals↗
PubMed1986

Influenza virus-specific antibody-secreting cells in the murine lung during primary influenza virus infection.

An enzyme-linked immunosorbent plaque assay is described which can reliably enumerate influenza virus-specific antibody-secreting cells and exhibits specificity similar to that of the indirect enzyme-linked immunosorbent assay. The assay was used to characterize the development of specific antibody-secreting cells, principally within lung tissue, during primary murine influenza virus infection after intranasal inoculation. Cells secreting influenza virus-specific immunoglobulin M (IgM), IgG, and IgA were detected in greatest numbers in lung tissue, and the data presented indicated that the cells may have originated from specific B-cell precursors in lung tissue which are demonstratable in vitro. At 11 months after infection, cells secreting IgG and IgA were still present in lung tissue. Influenza virus-specific antibody-secreting cells were also detected in spleen tissue and blood. Antibody-secreting cells appeared earlier in spleen than in lung tissue and declined more rapidly in spleen tissue.

Animals↗
PubMed1985

The generation of effector T cells in influenza A-infected, cyclosporine A-treated mice.

Specific effector T cells that mediate DTH to influenza virus were found to be formed in vivo in CsA-treated mice. The activity of these cells could only be measured when they were transferred into untreated naive mice. The cells mediating DTH were H-2 restricted in the I region of the MHC. When effector T cells that mediated DTH were transferred into CsA-treated recipients, no DTH activity could be detected. Influenza-specific cytotoxic T cells could not be detected in the spleens of CsA-treated mice given virus intravenously, even when drug treatment was started 3 days after virus administration. There was only a partial restoration of cytotoxic activity when spleen cells from CsA-treated infected mice were cultured in the presence of virus-infected stimulators. This seemed to indicate that Class I-restricted responses were more susceptible to CsA than the generation of Class II (or I-region-restricted) responses.

Animals↗
PubMed1985

In vivo effects of cyclosporine on influenza A virus-infected mice.

Cyclosporine (cyclosporin A, CsA) administered to mice substantially affects their immune response to an influenza A virus infection. If treated with CsA for 21 days, the mouse lungs contain high titers of virus which are cleared more slowly than in controls. Indicators of pathological damage--lung weight, extent of consolidation, fine morphology, and the extent of infiltration of dividing cells into the lung--showed that administration of CsA greatly decreased the level of inflammation. The production of hemagglutination-inhibiting (HI) antibody was delayed but reached almost control levels and NK cell activity in the lung was also comparable to control levels. In contrast, a delayed-type hypersensitivity (DTH) response to the virus could not be elicited in the CsA-treated, infected mice at 6 or 12 days after infection. Cytotoxic-T-cell (Tc-cell) activity was present in the lungs of such mice though its appearance was delayed and the activity recovered was less than that of the control infected mice. If administered with a dose of virus lethal for normal mice. CSA-treated mice survived, probably due to the greatly reduced level of immunopathological damage in the infected lung.

Animals↗