Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model
<p>Abstract</p> <p>Background</p> <p>Current data suggest that an efficacious human immunodeficiency virus type 1 (HIV-1) vaccine should elicit both adaptive humoral and cell mediated immune responses. Such a vaccine will also need to protect against infection from a ra...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-07-01
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| Series: | Retrovirology |
| Subjects: | |
| Online Access: | http://www.retrovirology.com/content/9/1/56 |
| _version_ | 1811319211997265920 |
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| author | Page Mark Stebbings Richard Berry Neil Hull Robin Ferguson Deborah Davis Leanne Duffy Laura Elsley William Hall Joanna Ham Claire Hassall Mark Li Bo Mee Edward T Quartey-Papafio Ruby Rose Nicola J Mathy Nathalie Voss Gerald Stott E Almond Neil |
| author_facet | Page Mark Stebbings Richard Berry Neil Hull Robin Ferguson Deborah Davis Leanne Duffy Laura Elsley William Hall Joanna Ham Claire Hassall Mark Li Bo Mee Edward T Quartey-Papafio Ruby Rose Nicola J Mathy Nathalie Voss Gerald Stott E Almond Neil |
| author_sort | Page Mark |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Current data suggest that an efficacious human immunodeficiency virus type 1 (HIV-1) vaccine should elicit both adaptive humoral and cell mediated immune responses. Such a vaccine will also need to protect against infection from a range of heterologous viral variants. Here we have developed a simian-human immunodeficiency virus (SHIV) based model in cynomolgus macaques to investigate the breadth of protection conferred by HIV-1<sub>W61D</sub> recombinant gp120 vaccination against SHIV<sub>sbg</sub> and SHIV<sub>SF33</sub> challenge, and to identify correlates of protection.</p> <p>Results</p> <p>High titres of anti-envelope antibodies were detected in all vaccinees. The antibodies reacted with both the homologous HIV-1<sub>W61D</sub> and heterologous HIV-1<sub>IIIB</sub> envelope rgp120 which has an identical sequence to the SHIV<sub>sbg</sub> challenge virus. Significant titres of virus neutralising antibodies were detected against SHIV<sub>W61D</sub> expressing an envelope homologous with the vaccine, but only limited cross neutralisation against SHIV<sub>sbg</sub>, SHIV-4 and SHIV<sub>SF33</sub> was observed. Protection against SHIV<sub>sbg</sub> infection was observed in vaccinated animals but none was observed against SHIV<sub>SF33</sub> challenge. Transfer of immune sera from vaccinated macaques to naive recipients did not confer protection against SHIV<sub>sbg</sub> challenge. In a follow-up study, T cell proliferative responses detected after immunisation with the same vaccine against a single peptide present in the second conserved region 2 of HIV-1 <sub>W61D</sub> and HIV-1 IIIB gp120, but not SF33 gp120.</p> <p>Conclusions</p> <p>Following extended vaccination with a HIV-1 rgp120 vaccine, protection was observed against heterologous virus challenge with SHIV<sub>sbg</sub>, but not SHIV<sub>SF33</sub>. Protection did not correlate with serological responses generated by vaccination, but might be associated with T cell proliferative responses against an epitope in the second constant region of HIV-1 gp120. Broader protection may be obtained with recombinant HIV-1 envelope based vaccines formulated with adjuvants that generate proliferative T cell responses in addition to broadly neutralising antibodies.</p> |
| first_indexed | 2024-04-13T12:38:55Z |
| format | Article |
| id | doaj.art-30306053a583405fb93b834bc3d0e7c2 |
| institution | Directory Open Access Journal |
| issn | 1742-4690 |
| language | English |
| last_indexed | 2024-04-13T12:38:55Z |
| publishDate | 2012-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Retrovirology |
| spelling | doaj.art-30306053a583405fb93b834bc3d0e7c22022-12-22T02:46:35ZengBMCRetrovirology1742-46902012-07-01915610.1186/1742-4690-9-56Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque modelPage MarkStebbings RichardBerry NeilHull RobinFerguson DeborahDavis LeanneDuffy LauraElsley WilliamHall JoannaHam ClaireHassall MarkLi BoMee Edward TQuartey-Papafio RubyRose Nicola JMathy NathalieVoss GeraldStott EAlmond Neil<p>Abstract</p> <p>Background</p> <p>Current data suggest that an efficacious human immunodeficiency virus type 1 (HIV-1) vaccine should elicit both adaptive humoral and cell mediated immune responses. Such a vaccine will also need to protect against infection from a range of heterologous viral variants. Here we have developed a simian-human immunodeficiency virus (SHIV) based model in cynomolgus macaques to investigate the breadth of protection conferred by HIV-1<sub>W61D</sub> recombinant gp120 vaccination against SHIV<sub>sbg</sub> and SHIV<sub>SF33</sub> challenge, and to identify correlates of protection.</p> <p>Results</p> <p>High titres of anti-envelope antibodies were detected in all vaccinees. The antibodies reacted with both the homologous HIV-1<sub>W61D</sub> and heterologous HIV-1<sub>IIIB</sub> envelope rgp120 which has an identical sequence to the SHIV<sub>sbg</sub> challenge virus. Significant titres of virus neutralising antibodies were detected against SHIV<sub>W61D</sub> expressing an envelope homologous with the vaccine, but only limited cross neutralisation against SHIV<sub>sbg</sub>, SHIV-4 and SHIV<sub>SF33</sub> was observed. Protection against SHIV<sub>sbg</sub> infection was observed in vaccinated animals but none was observed against SHIV<sub>SF33</sub> challenge. Transfer of immune sera from vaccinated macaques to naive recipients did not confer protection against SHIV<sub>sbg</sub> challenge. In a follow-up study, T cell proliferative responses detected after immunisation with the same vaccine against a single peptide present in the second conserved region 2 of HIV-1 <sub>W61D</sub> and HIV-1 IIIB gp120, but not SF33 gp120.</p> <p>Conclusions</p> <p>Following extended vaccination with a HIV-1 rgp120 vaccine, protection was observed against heterologous virus challenge with SHIV<sub>sbg</sub>, but not SHIV<sub>SF33</sub>. Protection did not correlate with serological responses generated by vaccination, but might be associated with T cell proliferative responses against an epitope in the second constant region of HIV-1 gp120. Broader protection may be obtained with recombinant HIV-1 envelope based vaccines formulated with adjuvants that generate proliferative T cell responses in addition to broadly neutralising antibodies.</p>http://www.retrovirology.com/content/9/1/56Envelope HIV-1 vaccineRecombinant gp120Macaque modelSHIVHeterologous challengeProtectionCynomolgus macaque |
| spellingShingle | Page Mark Stebbings Richard Berry Neil Hull Robin Ferguson Deborah Davis Leanne Duffy Laura Elsley William Hall Joanna Ham Claire Hassall Mark Li Bo Mee Edward T Quartey-Papafio Ruby Rose Nicola J Mathy Nathalie Voss Gerald Stott E Almond Neil Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model Retrovirology Envelope HIV-1 vaccine Recombinant gp120 Macaque model SHIV Heterologous challenge Protection Cynomolgus macaque |
| title | Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model |
| title_full | Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model |
| title_fullStr | Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model |
| title_full_unstemmed | Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model |
| title_short | Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model |
| title_sort | heterologous protection elicited by candidate monomeric recombinant hiv 1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model |
| topic | Envelope HIV-1 vaccine Recombinant gp120 Macaque model SHIV Heterologous challenge Protection Cynomolgus macaque |
| url | http://www.retrovirology.com/content/9/1/56 |
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