Dataset Information

Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model.

ABSTRACT:

Background

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-1W61D recombinant gp120 vaccination against SHIVsbg and SHIVSF33 challenge, and to identify correlates of protection.

Results

High titres of anti-envelope antibodies were detected in all vaccinees. The antibodies reacted with both the homologous HIV-1W61D and heterologous HIV-1IIIB envelope rgp120 which has an identical sequence to the SHIVsbg challenge virus. Significant titres of virus neutralising antibodies were detected against SHIVW61D expressing an envelope homologous with the vaccine, but only limited cross neutralisation against SHIVsbg, SHIV-4 and SHIVSF33 was observed. Protection against SHIVsbg infection was observed in vaccinated animals but none was observed against SHIVSF33 challenge. Transfer of immune sera from vaccinated macaques to naive recipients did not confer protection against SHIVsbg 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 W61D and HIV-1 IIIB gp120, but not SF33 gp120.

Conclusions

Following extended vaccination with a HIV-1 rgp120 vaccine, protection was observed against heterologous virus challenge with SHIVsbg, but not SHIVSF33. 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.

SUBMITTER: Page M

PROVIDER: S-EPMC3418562 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Publications

Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model.

Page Mark M Stebbings Richard R Berry Neil N Hull Robin R Ferguson Deborah D Davis Leanne L Duffy Laura L Elsley William W Hall Joanna J Ham Claire C Hassall Mark M Li Bo B Mee Edward T ET Quartey-Papafio Ruby R Rose Nicola J NJ Mathy Nathalie N Voss Gerald G Stott E James EJ Almond Neil N

Retrovirology 20120716

<h4>Background</h4>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-1W61D recombinant gp120 vaccination against SHIVsbg ...[more]

PMID: 22799593

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Project description:Gammacoronavirus infectious bronchitis virus (IBV) causes an economically important respiratory disease of poultry. Protective immunity is associated with the major structural protein, spike (S) glycoprotein, which induces neutralising antibodies and defines the serotype. Cross-protective immunity between serotypes is limited and can be difficult to predict. In this study, the ability of two recombinant IBV vaccine candidates, BeauR-M41(S) and BeauR-4/91(S), to induce cross-protection against a third serotype, QX, was assessed. Both rIBVs are genetically based on the Beaudette genome with only the S gene derived from either M41 or 4/91, two unrelated serotypes. The use of these rIBVs allowed for the assessment of the potential of M41 and 4/91 S glycoproteins to induce cross-protective immunity against a heterologous QX challenge. The impact of the order of vaccination was also assessed. Homologous primary and secondary vaccination with BeauR-M41(S) or BeauR-4/91(S) resulted in a significant reduction of infectious QX load in the trachea at four days post-challenge, whereas heterologous primary and secondary vaccination with BeauR-M41(S) and BeauR-4/91(S) reduced viral RNA load in the conjunctiva-associated lymphoid tissue (CALT). Both homologous and heterologous vaccination regimes reduced clinical signs and birds recovered more rapidly as compared with an unvaccinated/challenge control group. Despite both rIBV BeauR-M41(S) and BeauR-4/91(S) displaying limited replication in vivo, serum titres in these vaccinated groups were higher as compared with the unvaccinated/challenge control group. This suggests that vaccination with rIBV primed the birds for a boosted humoral response to heterologous QX challenge. Collectively, vaccination with the rIBV elicited limited protection against challenge, with failure to protect against tracheal ciliostasis, clinical manifestations, and viral replication. The use of a less attenuated recombinant vector that replicates throughout the respiratory tract could be required to elicit a stronger and prolonged protective immune response.

Dataset Information

Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model.

Background

Results

Conclusions

Publications

Heterologous protection elicited by candidate monomeric recombinant HIV-1 gp120 vaccine in the absence of cross neutralising antibodies in a macaque model.

Similar Datasets

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