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Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
The simian immunodeficiency virus transmembrane protein is poorly immunogenic in inactivated virus vaccine
M P Cranage1, B W McBride, E W Rud
1Centre for Applied Microbiology and Research, Porton Down, Salisbury, UK.
Abstract:
The transmembrane proteins (TMP) of immunodeficiency lentiviruses are primary candidates for inclusion in AIDS vaccines, the design and testing of which is facilitated by the SIV-macaque infection model. Antibody responses to linear determinants in the SIVmac TMP were investigated in rhesus macaques either infected with the SIVmac J5 molecular clone or vaccinated with partially purified, formalin-inactivated SIVmac. Infected animals were shown to recognise predominantly four regions in the external domain and three regions in the internal domain of the TMP defined by a series of nominally 20mer overlapping peptides. In contrast SIV vaccinates had extremely restricted and weak antibody responses to the TMP, indicating a selective loss of immunogenicity of this component in the vaccine.
Insights
Antibody responses to simian immunodeficiency virus (SIV) transmembrane proteins (TMP) were studied in macaques. Infected macaques recognized multiple TMP regions, while SIV vaccine recipients showed weak responses, suggesting reduced immunogenicity in vaccines.
Area of Science:
- Immunology
- Virology
- Vaccine Development
Background:
- Transmembrane proteins (TMP) of immunodeficiency lentiviruses are key targets for AIDS vaccine design.
- The SIV-macaque model is crucial for evaluating vaccine candidates and understanding immune responses.
- Investigating antibody recognition of SIV TMP is vital for improving vaccine efficacy.
Purpose of the Study:
- To investigate antibody responses to linear determinants within the SIVmac TMP.
- To compare immune recognition of TMP in SIV-infected versus SIV-vaccinated macaques.
Main Methods:
- Rhesus macaques were infected with SIVmac or vaccinated with inactivated SIVmac.
- Antibody responses were assessed against a series of overlapping 20-mer peptides representing SIVmac TMP.
Main Results:
- Infected macaques recognized multiple linear epitopes in both external and internal TMP domains.
- SIV vaccine recipients exhibited highly restricted and weak antibody responses to TMP.
- Formalin inactivation of SIVmac significantly diminished the immunogenicity of TMP.
Conclusions:
- The immunogenicity of SIV transmembrane proteins is selectively lost during vaccine preparation.
- Current SIV vaccine strategies may fail to elicit robust antibody responses against critical TMP epitopes.
- Further research is needed to enhance TMP immunogenicity in future AIDS vaccine designs.
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