Immunogenicity of HIV-1 Vaccines Expressing Chimeric Envelope Glycoproteins on the Surface of Pr55 Gag Virus-Like Particles
The HIV-1 envelope glycoprotein (Env) is present on the surface of the virion at a very low density compared to most other enveloped viruses. Substitution of various parts of the stalk domain of Env (gp41) with the corresponding elements from other viral glycoproteins has been shown to increase Env...
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| Format: | Article |
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MDPI AG
2020-01-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/8/1/54 |
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| author | Rosamund Chapman Michiel van Diepen Shireen Galant Elizabeth Kruse Emmanuel Margolin Phindile Ximba Tandile Hermanus Penny Moore Nicola Douglass Anna-Lise Williamson Edward Rybicki |
| author_facet | Rosamund Chapman Michiel van Diepen Shireen Galant Elizabeth Kruse Emmanuel Margolin Phindile Ximba Tandile Hermanus Penny Moore Nicola Douglass Anna-Lise Williamson Edward Rybicki |
| author_sort | Rosamund Chapman |
| collection | DOAJ |
| description | The HIV-1 envelope glycoprotein (Env) is present on the surface of the virion at a very low density compared to most other enveloped viruses. Substitution of various parts of the stalk domain of Env (gp41) with the corresponding elements from other viral glycoproteins has been shown to increase Env spike density on the cell membrane and surface of virus-like particles (VLPs). In this study, chimeric Env antigens were generated by replacing the transmembrane and cytoplasmic domains of HIV-1 Env with the corresponding regions from the influenza H5 hemagglutinin (HA) (gp140HA<sub>2</sub>tr) and by replacing the entire gp41 region of Env with the HA<sub>2</sub> subunit of HA (gp120HA<sub>2</sub>). Recombinant DNA and modified vaccinia Ankara (MVA) vaccines expressing HIV-1 subtype C mosaic Gag and gp150 Env or either of the chimeras were generated. Surprisingly, no significant differences were found in the levels of expression of gp150 Env or either of the chimeras on the surface of cells or on Gag VLPs. Differences were, however, observed in the binding of different monoclonal antibodies to the HIV-1 Env. Monoclonal antibodies, which recognized a V1 / V2 quaternary epitope at the tip of the native Env trimer, bound gp150 and gp140HA<sub>2</sub>tr chimera but failed to bind to the gp120HA<sub>2</sub> chimera. Autologous Tier 2 neutralizing antibodies (NAbs) were produced by rabbits inoculated with DNA and MVA vaccines expressing the gp140HA<sub>2</sub>tr chimera or gp150 Env, but not those immunized with the gp120HA<sub>2</sub> Env. These results showed that the addition of an HA<sub>2</sub> stalk to HIV-1 gp120 did not improve immunogenicity, but rather that the full-length gp150 was required for optimal presentation of epitopes for the elicitation of a neutralizing antibody response to HIV-1. |
| first_indexed | 2024-04-11T13:18:47Z |
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| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-11T13:18:47Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
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| series | Vaccines |
| spelling | doaj.art-0cccae28b5a74ba797746701604ba33e2022-12-22T04:22:16ZengMDPI AGVaccines2076-393X2020-01-01815410.3390/vaccines8010054vaccines8010054Immunogenicity of HIV-1 Vaccines Expressing Chimeric Envelope Glycoproteins on the Surface of Pr55 Gag Virus-Like ParticlesRosamund Chapman0Michiel van Diepen1Shireen Galant2Elizabeth Kruse3Emmanuel Margolin4Phindile Ximba5Tandile Hermanus6Penny Moore7Nicola Douglass8Anna-Lise Williamson9Edward Rybicki10Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South AfricaDivision of Biomedical Engineering, Department of Human Biology, University of Cape Town, Cape Town 7925, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South AfricaCentre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South AfricaCentre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South AfricaInstitute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South AfricaThe HIV-1 envelope glycoprotein (Env) is present on the surface of the virion at a very low density compared to most other enveloped viruses. Substitution of various parts of the stalk domain of Env (gp41) with the corresponding elements from other viral glycoproteins has been shown to increase Env spike density on the cell membrane and surface of virus-like particles (VLPs). In this study, chimeric Env antigens were generated by replacing the transmembrane and cytoplasmic domains of HIV-1 Env with the corresponding regions from the influenza H5 hemagglutinin (HA) (gp140HA<sub>2</sub>tr) and by replacing the entire gp41 region of Env with the HA<sub>2</sub> subunit of HA (gp120HA<sub>2</sub>). Recombinant DNA and modified vaccinia Ankara (MVA) vaccines expressing HIV-1 subtype C mosaic Gag and gp150 Env or either of the chimeras were generated. Surprisingly, no significant differences were found in the levels of expression of gp150 Env or either of the chimeras on the surface of cells or on Gag VLPs. Differences were, however, observed in the binding of different monoclonal antibodies to the HIV-1 Env. Monoclonal antibodies, which recognized a V1 / V2 quaternary epitope at the tip of the native Env trimer, bound gp150 and gp140HA<sub>2</sub>tr chimera but failed to bind to the gp120HA<sub>2</sub> chimera. Autologous Tier 2 neutralizing antibodies (NAbs) were produced by rabbits inoculated with DNA and MVA vaccines expressing the gp140HA<sub>2</sub>tr chimera or gp150 Env, but not those immunized with the gp120HA<sub>2</sub> Env. These results showed that the addition of an HA<sub>2</sub> stalk to HIV-1 gp120 did not improve immunogenicity, but rather that the full-length gp150 was required for optimal presentation of epitopes for the elicitation of a neutralizing antibody response to HIV-1.https://www.mdpi.com/2076-393X/8/1/54hiv-1vaccinechimericvlpspike densityenvelope |
| spellingShingle | Rosamund Chapman Michiel van Diepen Shireen Galant Elizabeth Kruse Emmanuel Margolin Phindile Ximba Tandile Hermanus Penny Moore Nicola Douglass Anna-Lise Williamson Edward Rybicki Immunogenicity of HIV-1 Vaccines Expressing Chimeric Envelope Glycoproteins on the Surface of Pr55 Gag Virus-Like Particles Vaccines hiv-1 vaccine chimeric vlp spike density envelope |
| title | Immunogenicity of HIV-1 Vaccines Expressing Chimeric Envelope Glycoproteins on the Surface of Pr55 Gag Virus-Like Particles |
| title_full | Immunogenicity of HIV-1 Vaccines Expressing Chimeric Envelope Glycoproteins on the Surface of Pr55 Gag Virus-Like Particles |
| title_fullStr | Immunogenicity of HIV-1 Vaccines Expressing Chimeric Envelope Glycoproteins on the Surface of Pr55 Gag Virus-Like Particles |
| title_full_unstemmed | Immunogenicity of HIV-1 Vaccines Expressing Chimeric Envelope Glycoproteins on the Surface of Pr55 Gag Virus-Like Particles |
| title_short | Immunogenicity of HIV-1 Vaccines Expressing Chimeric Envelope Glycoproteins on the Surface of Pr55 Gag Virus-Like Particles |
| title_sort | immunogenicity of hiv 1 vaccines expressing chimeric envelope glycoproteins on the surface of pr55 gag virus like particles |
| topic | hiv-1 vaccine chimeric vlp spike density envelope |
| url | https://www.mdpi.com/2076-393X/8/1/54 |
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