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Attenuated Mengo virus as a vector for immunogenic human immunodeficiency virus type 1 glycoprotein 120
R Altmeyer1, N Escriou, M Girard
1Unité de Virologie Moléculaire, Institut Pasteur, Paris, France.
Abstract:
Introduction of a sequence encoding 147 amino acids from human immunodeficiency virus type I (HIV-1) strain MN glycoprotein gp120 into the RNA genome of the stably attenuated Mengo virus strain vM16 yielded an infectious recombinant virus, vMLN450, which expressed the heterologous HIV-1 sequence along with the normal Mengo virus proteins. The HIV-1 gp120 sequence, fused to the amino terminus of the short, nonstructural Mengo virus leader polypeptide was recognized by a gp120 V3 loop-specific monoclonal antibody. When inoculated into mice, recombinant virus vMLN450 elicited a high-titer anti-HIV-1 antibody response as well as an HIV-1MN-specific cytotoxic cellular immune response. An anti-HIV-1 antibody response could also be detected in cynomolgus monkeys after a single immunization. We propose that attenuated Mengo virus can serve as an effective expression vector in cell systems and various animal species and offers another approach to the development of new, live recombinant vaccines.
Insights
Mengo virus was engineered to express HIV-1 glycoprotein gp120, creating a recombinant virus. This novel vaccine candidate successfully induced anti-HIV-1 immune responses in animal models.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Human immunodeficiency virus type I (HIV-1) remains a significant global health challenge.
- Development of effective vaccines against HIV-1 is crucial for disease control.
- Attenuated viruses offer potential as live vectors for vaccine development.
Purpose of the Study:
- To engineer a recombinant virus expressing HIV-1 glycoprotein gp120.
- To evaluate the immunogenicity of the recombinant virus in animal models.
- To assess the potential of attenuated Mengo virus as a vaccine vector.
Main Methods:
- A sequence encoding 147 amino acids of HIV-1 strain MN gp120 was inserted into the Mengo virus RNA genome.
- The resulting recombinant virus, vMLN450, was characterized for expression of the heterologous HIV-1 sequence.
- Mice and cynomolgus monkeys were inoculated with vMLN450 to assess immune responses.
Main Results:
- Infectious recombinant virus vMLN450 was successfully generated, expressing the HIV-1 gp120 sequence.
- The expressed gp120 sequence was recognized by a V3 loop-specific monoclonal antibody.
- Inoculation of vMLN450 elicited high-titer anti-HIV-1 antibody and HIV-1MN-specific cytotoxic cellular immune responses in mice.
- Anti-HIV-1 antibody responses were detected in monkeys after a single immunization.
Conclusions:
- Attenuated Mengo virus can serve as an effective expression vector in various cell systems and animal species.
- The recombinant virus vMLN450 demonstrates potential as a live recombinant vaccine candidate against HIV-1.
- This approach offers a novel strategy for developing new live recombinant vaccines.