Neutralizing antibodies induced by liposomal HIV-1 glycoprotein 41 peptide simultaneously bind to both the 2F5 or 4E10 epitope and lipid epitopes

Matyas, Gary R.; Wieczorek, Lindsay; Beck, Zoltán; Ochsenbauer-Jambor, Christina; Kappes, John C.; Michael, Nelson L.; Polonis, Victoria R.; Alving, Carl R.

doi:10.1097/qad.0b013e32832faea5

Cited by 69 publications

(53 citation statements)

References 52 publications

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“…Despite extensive analyses of the MPER peptides (5,36,47,49,79), the in vivo/in situ structure of this region of the Env spike is unknown for any stage of the prefusion/fusion sequence. The hydrophobic nature of the MPER suggests a significant association with the lipid bilayer (30,42,57,77).…”

Section: Discussionmentioning

confidence: 99%

Binding of Anti-Membrane-Proximal gp41 Monoclonal Antibodies to CD4-Liganded and -Unliganded Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus Virions

Rathinakumar

Dutta

Zhu

et al. 2012

J Virol

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Section: Discussionmentioning

confidence: 99%

Binding of Anti-Membrane-Proximal gp41 Monoclonal Antibodies to CD4-Liganded and -Unliganded Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus Virions

Rathinakumar

Dutta

Zhu

et al. 2012

J Virol

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“…The poor immunogenicity of this region may be attributed to its lack of exposure on the surface of the native virus (9,34,41,44; reviewed in reference 30). The neutralizing activity of these antibodies appears to be dependent on binding to both the MPER and to the viral membrane (25). It has been proposed that antibody binding to the viral membrane serves to concentrate the antibody in the region of the MPER, thereby favoring its interaction with this poorly exposed antigenic epitope (1).…”

Section: Vol 84 2010 Gp41 Epitope Mapping In Hiv-1 5037mentioning

confidence: 99%

Anti-gp41 Antibodies Cloned from HIV-Infected Patients with Broadly Neutralizing Serologic Activity

Pietzsch

Scheid

Mouquet

et al. 2010

J Virol

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Most HIV-infected individuals develop antibodies to the gp120 and gp41 components of the viral spike; however, only a fraction of these individuals mount a broadly neutralizing serum response against HIV. We have cloned anti-HIV antibodies from the memory B-cell compartment of six individuals with variable viral loads and high titers of broadly neutralizing antibodies. Here, we report on the features of the anti-gp41 response in these patients. Competition experiments with previously characterized antibodies targeting defined epitopes on the gp41 ectodomain showed antibodies directed against the "immunodominant region" (cluster I), the carboxy-terminal heptad repeat (cluster II), and the membrane-proximal external region (cluster IV). On the other hand, antibodies directed against the amino-terminal part of the molecule, including the fusion peptide, polar region, and the N-terminal heptad repeat, were not detected. When all patients' data were combined, unique B-cell clones targeting cluster I, II, and IV accounted for 32%, 49%, and 53% of all anti-gp41-reactive B cells, respectively; therefore, no single region was truly immunodominant. Finally, although we found no new neutralizing epitopes or HIV-1-neutralizing activity by any of the gp41 antibodies at concentrations of up to 50 g/ml, high concentrations of 7 out of 15 anti-cluster I antibodies neutralized tier 2 viruses.The trimeric envelope spike of the human immunodeficiency virus (HIV) consists of three heterodimers of the transmembrane glycoprotein (gp41) and the surface glycoprotein (gp120) (59). Whereas gp120 carries the CD4 and chemokine receptor binding sites, gp41 is crucial for fusion between the viral particle and the cell membrane (Fig. 1a). The glycine-rich fusion peptide, located at the amino-terminal region of gp41, is normally covered by gp120 but is transiently exposed for interaction with the target cell membrane when gp120 binds to its receptors (14). The fusion peptide is followed by a serine/ threonine-rich polar region and heptad repeats, which form leucine zippers that mediate assembly of the coiled-coiled form of gp41 in response to gp120 engagement (8,22,24,52). Finally, the membrane-proximal external region (MPER) also plays a role in virus-host membrane fusion (38); however, the mechanism by which it enhances fusion is not known.Some regions of gp41 are accessible to antibodies on the native gp140 trimer; however, others are exposed to the immune system only after gp120 shedding (40). In addition, otherwise cryptic gp41 epitopes are uncovered during viral fusion with the cell membrane (13). Consistent with gp41 exposure to the immune system, serologic studies of infected individuals indicate that there is a strong humoral response to gp41 during HIV infection (35) which precedes the response against gp120 (26).Antibodies to gp41 have been isolated from phage display libraries, as have Epstein-Barr virus (EBV) immortalized B cells from infected individuals (4, 53). Some of these anti-gp41 antibodies can neutralize HIV infection in ...

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“…The "flagpole"-like MPER structures repeated on the surface of negatively charged membranes, might additionally embody multivalent antigens for the efficient activation of B-cell receptors. Finally, these vesicles might provide a suitable environment for generating antibodies capable of binding heterotypically to peptide and lipid (9,31).…”

Section: Figure 8 Recovered Responses After Vaccination With the Popmentioning

confidence: 99%

“…2F5 was isolated in mAb form by Katinger and co-workers (21,22) from a panel of sera from naturally infected asymptomatic individuals. Given the neutralization breath and potency shown by the bNAb 2F5 (13,21,(23)(24)(25)(26), development of peptide-based vaccines targeting the 2F5 epitope has since been pursued (6,22,(27)(28)(29)(30)(31)(32)(33).…”

mentioning

confidence: 99%

Structure and Immunogenicity of a Peptide Vaccine, Including the Complete HIV-1 gp41 2F5 Epitope

Serrano

Araujo

Apellániz

et al. 2014

Journal of Biological Chemistry

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Background: HIV-1 vaccines should elicit broadly neutralizing antibodies as the gp41 "membrane-proximal external region" targeting MAb2F5. Results: NMR disclosed unprecedented 2F5 peptide-epitope structures. Although overall conformation was preserved in different adjuvants, recovered antibodies after vaccination were functionally different. Conclusion: Membrane-inserted helical oligomers may encompass effective 2F5 peptide vaccines. Significance: Disclosing the structures that generate 2F5-like antibodies may guide future vaccine development.

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Neutralizing antibodies induced by liposomal HIV-1 glycoprotein 41 peptide simultaneously bind to both the 2F5 or 4E10 epitope and lipid epitopes

Cited by 69 publications

References 52 publications

Binding of Anti-Membrane-Proximal gp41 Monoclonal Antibodies to CD4-Liganded and -Unliganded Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus Virions

Binding of Anti-Membrane-Proximal gp41 Monoclonal Antibodies to CD4-Liganded and -Unliganded Human Immunodeficiency Virus Type 1 and Simian Immunodeficiency Virus Virions

Anti-gp41 Antibodies Cloned from HIV-Infected Patients with Broadly Neutralizing Serologic Activity

Structure and Immunogenicity of a Peptide Vaccine, Including the Complete HIV-1 gp41 2F5 Epitope

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