Characterization of Monoclonal Antibodies to Human Immunodeficiency Virus Type 2 Envelope Glycoproteins

Traincard, François; Rey-Cuillé, Marie-Anne; Huon, Isabelle; Dartevelle, Sylvie; Mazié, J. C.; Bénichou, Serge

doi:10.1089/aid.1994.10.1659

Cited by 15 publications

(7 citation statements)

References 31 publications

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“…In accordance with the latter result, these anti‐peptide antibodies also failed to inhibit SIVmac251 replication in primary blood lymphocytes. These results agree with those reported for V3 of HIV‐2 by various groups61, 62 including ours63. However, using monoclonal or anti‐peptide antibody approaches, several neutralizing antibodies have been described and the recognized epitopes of some of them identified in the envelope glycoprotein sequence.…”

Section: Discussionsupporting

confidence: 91%

Structure‐antigenicity of the V3 region of SIVmac envelope glycoprotein

Gaston

Babas

Lakhdar-Ghazal

et al. 2009

Journal of Peptide Science

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The objective of this study was to analyze the immunogenicity and antigenicity of the V3 domain (Cys313-Cys346) of the external envelope glycoprotein gp125 of SIVmac251. The corresponding peptide was synthesized and characterized as linear and cyclic peptides. Our results showed that this region, as for HIV-1, contained an immunodominant epitope. The antigenicity was similar for the linear and cyclic peptides when tested against a panel of 15 sera from SIV infected macaques. Similarly, both peptide structures presented similar immunogenicity as shown by the characterization of the anti-peptide antibodies produced in rabbits against the cyclic and linear forms. But, unexpectedly, the antibodies produced against linear peptides recognized with a relatively higher intensity the native envelope gp140 than those produced against the cyclic structure. Furthermore, we showed that these antibodies recognized better the deglycosylated form of the glycoprotein. But, in contrast to the neutralizing activity obtained with anti-V3 peptides from HIV-1, no antiviral activity was obtained with antibodies generated against linear or cyclic SIVmac V3 peptides.

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Section: Discussionsupporting

confidence: 91%

Structure‐antigenicity of the V3 region of SIVmac envelope glycoprotein

Gaston

Babas

Lakhdar-Ghazal

et al. 2009

Journal of Peptide Science

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“…This region also contains major antigenic and neutralizing epitopes in HIV-1 which are well exposed upon CD4-binding [29], [30], [31], [32], [33], [34], [35]. Although still debatable, the V3 region in HIV-2 may also contain broadly neutralizing epitopes [36], [37], [38], [39], [40], [41], [42]. However, in contrast to HIV-1, the V3 and flanking C2 and C3 regions are not immunodominant in HIV-2 infected patients [43], [44], [45], [46].…”

Section: Introductionmentioning

confidence: 99%

Evolutionary and Structural Features of the C2, V3 and C3 Envelope Regions Underlying the Differences in HIV-1 and HIV-2 Biology and Infection

Barroso

Borrego²,

Bártolo

et al. 2011

PLoS ONE

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BackgroundUnlike in HIV-1 infection, the majority of HIV-2 patients produce broadly reactive neutralizing antibodies, control viral replication and survive as elite controllers. The identification of the molecular, structural and evolutionary footprints underlying these very distinct immunological and clinical outcomes may lead to the development of new strategies for the prevention and treatment of HIV infection.Methodology/Principal FindingsWe performed a side-by-side molecular, evolutionary and structural comparison of the C2, V3 and C3 envelope regions from HIV-1 and HIV-2. These regions contain major antigenic targets and are important for receptor binding. In HIV-2, these regions also have immune modulatory properties. We found that these regions are significantly more variable in HIV-1 than in HIV-2. Within each virus, C3 is the most entropic region followed by either C2 (HIV-2) or V3 (HIV-1). The C3 region is well exposed in the HIV-2 envelope and is under strong diversifying selection suggesting that, like in HIV-1, it may harbour neutralizing epitopes. Notably, however, extreme diversification of C2 and C3 seems to be deleterious for HIV-2 and prevent its transmission. Computer modelling simulations showed that in HIV-2 the V3 loop is much less exposed than C2 and C3 and has a retractile conformation due to a physical interaction with both C2 and C3. The concealed and conserved nature of V3 in the HIV-2 is consistent with its lack of immunodominancy in vivo and with its role in preventing immune activation. In contrast, HIV-1 had an extended and accessible V3 loop that is consistent with its immunodominant and neutralizing nature.Conclusions/SignificanceWe identify significant structural and functional constrains to the diversification and evolution of C2, V3 and C3 in the HIV-2 envelope but not in HIV-1. These studies highlight fundamental differences in the biology and infection of HIV-1 and HIV-2 and in their mode of interaction with the human immune system and may inform new vaccine and therapeutic interventions against these viruses.

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“…As for HIV-1, the antibody specificities that mediate HIV-2 neutralization and control are still elusive. The V3 region in the envelope gp125 has been identified as a neutralizing target by some but not by all investigators (3,6,7,11,40,47,54). Other weakly neutralizing epitopes were identified in the V1, V2, V4, and C5 regions in gp125 and in the COOH-terminal region of the gp41 ectodomain (6,7,41).…”

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confidence: 99%

Potent and Broadly Reactive HIV-2 Neutralizing Antibodies Elicited by a Vaccinia Virus Vector Prime-C2V3C3 Polypeptide Boost Immunization Strategy

Marcelino¹,

Borrego

Rocha

et al. 2010

J Virol

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Human immunodeficiency virus type 2 (HIV-2) infection affects about 1 to 2 million individuals, the majority living in West Africa, Europe, and India. As for HIV-1, new strategies for the prevention of HIV-2 infection are needed. Our aim was to produce new vaccine immunogens that elicit the production of broadly reactive HIV-2 neutralizing antibodies (NAbs). Native and truncated envelope proteins from the reference HIV-2ALI isolate were expressed in vaccinia virus or in bacteria. This source isolate was used due to its unique phenotype combining CD4 independence and CCR5 usage. NAbs were not elicited in BALB/c mice by single immunization with a truncated and fully glycosylated envelope gp125 (gp125t) or a recombinant polypeptide comprising the C2, V3, and C3 envelope regions (rpC2-C3). A strong and broad NAb response was, however, elicited in mice primed with gp125t expressed in vaccinia virus and boosted with rpC2-C3. Serum from these animals potently neutralized (median 50% neutralizing titer, 3,200) six of six highly divergent primary HIV-2 isolates. Coreceptor usage and the V3 sequence of NAb-sensitive isolates were similar to that of the vaccinating immunogen (HIV-2ALI). In contrast, NAbs were not reactive on three X4 isolates that displayed major changes in V3 loop sequence and structure. Collectively, our findings demonstrate that broadly reactive HIV-2 NAbs can be elicited by using a vaccinia virus vector-prime/rpC2-C3-boost immunization strategy and suggest a potential relationship between escape to neutralization and cell tropism.

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Characterization of Monoclonal Antibodies to Human Immunodeficiency Virus Type 2 Envelope Glycoproteins

Cited by 15 publications

References 31 publications

Structure‐antigenicity of the V3 region of SIVmac envelope glycoprotein

Structure‐antigenicity of the V3 region of SIVmac envelope glycoprotein

Evolutionary and Structural Features of the C2, V3 and C3 Envelope Regions Underlying the Differences in HIV-1 and HIV-2 Biology and Infection

Potent and Broadly Reactive HIV-2 Neutralizing Antibodies Elicited by a Vaccinia Virus Vector Prime-C2V3C3 Polypeptide Boost Immunization Strategy

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