Immunogenicity of HIV-1 Vaccines Expressing Chimeric Envelope Glycoproteins on the Surface of Pr55 Gag Virus-Like Particles

Rosamund Chapman; Michiel van Diepen; Shireen Galant; Elizabeth Kruse; Emmanuel Margolin; Phindile Ximba; Tandile Hermanus; Penny Moore; Nicola Douglass; Anna-Lise Williamson; Edward Rybicki

doi:10.3390/vaccines8010054

Immunogenicity of HIV-1 Vaccines Expressing Chimeric Envelope Glycoproteins on the Surface of Pr55 Gag Virus-Like Particles

Vaccines (Basel). 2020 Jan 29;8(1):54. doi: 10.3390/vaccines8010054.

Authors

Rosamund Chapman^{1

2}, Michiel van Diepen^{1

2}, Shireen Galant^{1

2}, Elizabeth Kruse³, Emmanuel Margolin^{1

2

4}, Phindile Ximba^{1

2}, Tandile Hermanus^{5

6}, Penny Moore^{5

6

7}, Nicola Douglass^{1

2}, Anna-Lise Williamson^{1

2}, Edward Rybicki^{1

4}

Affiliations

¹ Institute of Infectious Disease and Molecular Medicine, Faculty of Health Science, University of Cape Town, Cape Town 7925, South Africa.
² Division of Medical Virology, Department of Pathology, University of Cape Town, Cape Town 7925, South Africa.
³ Division of Biomedical Engineering, Department of Human Biology, University of Cape Town, Cape Town 7925, South Africa.
⁴ Biopharming Research Unit, Department of Molecular and Cell Biology, University of Cape Town, Cape Town 7701, South Africa.
⁵ Centre for HIV and STIs, National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa.
⁶ Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2050, South Africa.
⁷ Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Congella, Durban 4013, South Africa.

Abstract

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) (gp140HA₂tr) and by replacing the entire gp41 region of Env with the HA₂ subunit of HA (gp120HA₂). 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 gp140HA₂tr chimera but failed to bind to the gp120HA₂ chimera. Autologous Tier 2 neutralizing antibodies (NAbs) were produced by rabbits inoculated with DNA and MVA vaccines expressing the gp140HA₂tr chimera or gp150 Env, but not those immunized with the gp120HA₂ Env. These results showed that the addition of an HA₂ 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.

Keywords: HIV-1; VLP; chimeric; envelope; spike density; vaccine.