Antibodies Generated in Cats by a Lipopeptide Reproducing the Membrane-Proximal External Region of the Feline Immunodeficiency Virus Transmembrane Enhance Virus Infectivity

Giannecchini, Simone; D’Ursi, Anna Maria; Esposito, Cinzia; Scrima, Mario; Zabogli, Elisa; Freer, Giulia; Rovero, Paolo; Bendinelli, Mauro

doi:10.1128/cvi.00140-07

Cited by 11 publications

(17 citation statements)

References 60 publications

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“…This remains a challenge, and further work is needed to achieve the correct structure. Our strategy is analogous to that reported by Giannecchini and colleagues, in which octadecanoic acid was attached to the C terminus of MPR of feline immunodeficiency virus [44]. However, this immunogen elicited only weak anti-peptide antibodies (ELISA OD < 1.0 at 1:100 serum dilution) in cats.…”

Section: Discussionmentioning

confidence: 82%

Role of lipid structure in the humoral immune response in mice to covalent lipid–peptides from the membrane proximal region of HIV-1 gp41

Watson

Szoka

2009

Vaccine

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The membrane proximal region (MPR) of HIV-1 gp41 is a desirable target for development of a vaccine that elicits neutralizing antibodies since the patient-derived monoclonal antibodies, 2F5 and 4E10, bind to the MPR and neutralize primary HIV isolates. The 2F5 and 4E10 antibodies crossreact with lipids and structural studies suggest that MPR immunogens may be presented in a membrane environment. We hypothesized that covalent attachment of lipid anchors would enhance the humoral immune response to MPR-derived peptides presented in liposomal bilayers. In a comparison of eight lipids conjugated to an extended 2F5 epitope peptide, a sterol, cholesterol hemisuccinate (CHEMS), was found to promote the strongest anti-peptide IgG titers (6.4 × 10 4 ) in sera of BALB/C mice. Two lipid anchors, palmitic acid and phosphatidylcholine, failed to elicit a detectable serum anti-peptide IgG response. Association with the liposomal vehicle contributed to the ability of a lipopeptide to elicit anti-peptide antibodies, but no other single factor, such as position of the lipid anchor, peptide helical content, lipopeptide partition coefficient, or presence of phosphate on the anchor clearly determined lipopeptide potency. Conjugation to CHEMS also rendered a 4E10 epitope peptide immunogenic (5.6 × 10 2 IgG titer in serum). Finally, attachment of CHEMS to a peptide spanning both the 2F5 and 4E10 epitopes elicited serum IgG antibodies that bound to each of the individual epitopes as well as to recombinant gp140. Further research into the mechanism of how structure influences the immune response to the MPR may lead to immunogens that could be useful in prime-boost regimens for focusing the immune response in an HIV vaccine.

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Section: Discussionmentioning

confidence: 82%

Role of lipid structure in the humoral immune response in mice to covalent lipid–peptides from the membrane proximal region of HIV-1 gp41

Watson

Szoka

2009

Vaccine

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“…Furthermore, this approach may result in unintended consequences, as was observed for a lipidated peptide immunogen bearing the MPER sequence from feline immunodeficiency virus. When this peptide was displayed in multilamellar lipid vesicles and used as an immunogen in cats, the resulting Abs enhanced infection in an in vitro neutralization assay (80). In addition, studies described previously (92,124,131,134,144) did not map Ab specificities or correlate neutralization activity to specific epitopes.…”

Section: Should Mper-targeting Vaccines Be Presented In the Context Omentioning

confidence: 99%

The Membrane-Proximal External Region of the Human Immunodeficiency Virus Type 1 Envelope: Dominant Site of Antibody Neutralization and Target for Vaccine Design

Montero¹,

Houten

Wang³

et al. 2008

Microbiol Mol Biol Rev

234

194

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SUMMARY Enormous efforts have been made to produce a protective vaccine against human immunodeficiency virus type 1; there has been little success. However, the identification of broadly neutralizing antibodies against epitopes on the highly conserved membrane-proximal external region (MPER) of the gp41 envelope protein has delineated this region as an attractive vaccine target. Furthermore, emerging structural information on the MPER has provided vaccine designers with new insights for building relevant immunogens. This review describes the current state of the field regarding (i) the structure and function of the gp41 MPER; (ii) the structure and binding mechanisms of the broadly neutralizing antibodies 2F5, 4E10, and Z13; and (iii) the development of an MPER-targeting vaccine. In addition, emerging approaches to vaccine design are presented.

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“…A corollary finding of the present study was that in the vaccinees, the extent of control of FIV replication, as deduced from the reduced viral loads in plasma, correlated with the titer of NA present in the animals. This adds to the substantial body of evidence collected in recent years indicating that although it most likely acts in concert with other immune effectors, NA exerts a crucial role in immune protection against lentiviruses (20,25,28,39,40,59,63). Indeed, the development of immunogens capable of eliciting NA remains an important focus of current AIDS vaccine research (3,11,(28)(29)(30)59).…”

Section: Vol 84 2010mentioning

confidence: 99%

Env-Expressing Autologous T Lymphocytes Induce Neutralizing Antibody and Afford Marked Protection against Feline Immunodeficiency Virus

Pistello

Bonci

Zabogli

et al. 2010

J Virol

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The envelope (Env) glycoproteins of HIV and other lentiviruses possess neutralization and other protective epitopes, yet all attempts to induce protective immunity using Env as the only immunogen have either failed or afforded minimal levels of protection. In a novel prime-boost approach, specific-pathogen-free cats were primed with a plasmid expressing Env of feline immunodeficiency virus (FIV) and feline granulocyte-macrophage colony-stimulating factor and then boosted with their own T lymphocytes transduced ex vivo to produce the same Env and interleukin 15 (3 ؋ 10 6 to 10 ؋ 10 6 viable cells/cat). After the boost, the vaccinees developed elevated immune responses, including virus-neutralizing antibodies (NA). Challenge with an ex vivo preparation of FIV readily infected all eight control cats (four mock vaccinated and four naïve) and produced a marked decline in the proportion of peripheral CD4 T cells. In contrast, five of seven vaccinees showed little or no traces of infection, and the remaining two had reduced viral loads and underwent no changes in proportions of CD4 T cells. Interestingly, the viral loads of the vaccinees were inversely correlated to the titers of NA. The findings support the concept that Env is a valuable immunogen but needs to be administered in a way that permits the expression of its full protective potential.

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Antibodies Generated in Cats by a Lipopeptide Reproducing the Membrane-Proximal External Region of the Feline Immunodeficiency Virus Transmembrane Enhance Virus Infectivity

Cited by 11 publications

References 60 publications

Role of lipid structure in the humoral immune response in mice to covalent lipid–peptides from the membrane proximal region of HIV-1 gp41

Role of lipid structure in the humoral immune response in mice to covalent lipid–peptides from the membrane proximal region of HIV-1 gp41

The Membrane-Proximal External Region of the Human Immunodeficiency Virus Type 1 Envelope: Dominant Site of Antibody Neutralization and Target for Vaccine Design

Env-Expressing Autologous T Lymphocytes Induce Neutralizing Antibody and Afford Marked Protection against Feline Immunodeficiency Virus

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