Characterization of neutralizing monoclonal antibodies to linear and conformation-dependent epitopes within the first and second variable domains of human immunodeficiency virus type 1 gp120

McKeating, J.A.; Shotton, C; Cordell, Jacqueline; Graham, Susan M.; Balfe, Peter; Sullivan, Nancy; Charles, Marie‐Hélène; Page, Mark; Bolmstedt, Anders; Olofsson, Sigvard

doi:10.1128/jvi.67.8.4932-4944.1993

Cited by 135 publications

(90 citation statements)

References 58 publications

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“…The MoAbs used in this study are listed below, with their epitopes shown in brackets after the clone nomenclature: 11/65a (C1-aa102-121); 11/41a (C5-aa471-491); 11/4c (V2-aa152-181) [4,5]; 11/68b (V1/V2 discontinuous) [4,5]; 10/36c (V3-aa311-321); 10/54ow (V3-aa311-321); 11/85b (V3-aa311-321); ICR41 (V3-discontinuous); ICR38.1a (C4-aa427-436) [6]; ICR39.13 g (CD4 binding site discontinuous) [7] and 8/19b (gp120 discontinuous) [8].…”

Section: Gp120 Antigens and Monoclonal Antibodiesmentioning

confidence: 99%

“…Finally, sera were tested for reactivity with a truncated gp120 molecule containing the N-terminal and V1/V2 regions of the envelope protein [5]. It is interesting to note that the V1/V2 region has been reported to be a target for neutralizing antibodies and is immunogenic in infected individuals [4]. A very restricted number of sera from the protein-immunized animals contained V1/V2 reactivity, while none of the sera from the DNA immunized mice contained detectable antibody levels (data not shown).…”

Section: Comparison Of the Immune Response Following Dna And Protein mentioning

confidence: 99%

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Comparison of nucleic acid and protein immunization for induction of antibodies specific for HIV-1 gp120

Peet¹,

McKeating

Ramos³

et al. 1997

Clinical and Experimental Immunology

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SUMMARYWe have compared the antibody response to HIV-1 gp120 type LAI in mice immunized with either a gp120 expression plasmid or with baculovirus-derived recombinant gp120 (rgp120) formulated with Freund's complete adjuvant, TiterMax, Alum, Ribi R-700, AF-A or QuilA. DNA immunization resulted in variable levels of antibody, with endpoint titres ranging from 10 4 to 10 5 , whereas mice immunized with rgp120 mixed with Ribi R-700, AF-A or QuilA produced antibody levels with endpoint titres > 10 5 . Both types of immunization failed to elicit antibodies able to recognize denatured rgp120. The V3 region was immunogenic in animals immunized with nucleic acid, whereas only a few animals immunized with recombinant protein produced antibodies specific for V3 or other linear epitopes, irrespective of the adjuvant used. These data suggest that the immunogenicity of gp120 is dependent upon the mode of antigen delivery, and that in vivo expressed gp120 following nucleic acid immunization elicits, at least with respect to V3, an antibody response which more closely reflects that seen following natural infection in man.

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Section: Gp120 Antigens and Monoclonal Antibodiesmentioning

confidence: 99%

Section: Comparison Of the Immune Response Following Dna And Protein mentioning

confidence: 99%

Comparison of nucleic acid and protein immunization for induction of antibodies specific for HIV-1 gp120

Peet¹,

McKeating

Ramos³

et al. 1997

Clinical and Experimental Immunology

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“…Antibodies directed against V2 and V3 in general have potent virus-neutralizing capacity (Fung et al 1992, McKeating et al 1993. It is of interest that the predicted conformational changes between NSI and SI variants may affect antibody recognition which may provide SI variants with an escape from neutralizing antibodies.…”

Section: Virus Phenotype Evolutionmentioning

confidence: 99%

Changing Virus‐Host Interactions in the Course of HIV‐1 Infection

Miedema

Meyaard

Koot

et al. 1994

Immunological Reviews

144

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“…In the present study, the frequency of plasma anti-V2 Abs was between 53% and 85% for the three V1V2 fusion proteins and was comparable to results in the RV144 study, which reported 84% frequency, possibly due to using the same V1V2 fusion proteins for screening (9). In previous studies of sera of individuals chronically infected with HIV-1, anti-V2 Abs were detected at a much lower frequency (from 12% to 48%), but either the V2 antigens tested were different or plasma Abs were analyzed by different methods (4–7).…”

Section: Discussionmentioning

confidence: 90%

“…The frequency of anti-V2 Abs in the plasma of individuals infected with HIV-1 varies among studies, depending on the methods used and the population studied. Screening of immune plasma using V2 consensus peptides with the HxB2 sequence detected 12% and 21% positive sera from HIV-1-infected individuals (4, 5). Using V1V2 proteins expressing both conformation-dependent V2i and linear V2p epitopes, the frequency of plasma anti-V2 Abs is higher, yielding 30% and 48% in two studies (6, 7).…”

mentioning

confidence: 99%

Anti-V2 Antibody Deficiency in Individuals Infected With HIV-1

Liu

Nanfack

et al. 2018

Preprint

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25The positive correlation of high levels of plasma anti-V2 antibodies (Abs) with protective 26 immunity in the Phase III anti-HIV RV144 vaccine trial generated interest in the induction of 27 these Abs for HIV vaccine development. We analyzed plasma samples from 79 chronically 28 infected Cameroonian individuals for Ab reactivity against three V1V2 fusion proteins and five 29 cyclic V2 peptides and found that HIV-1 infection induces different levels of anti-V2 Abs. While 30 the majority of plasma samples reacted strongly with one or more V2 antigens, 10% (8) of the 31 samples were nonreactive. Deficiency of anti-V2 Abs was consistently found in longitudinal 32 plasma samples tested over 8 to 54 months of HIV infection. There was a strong correlation 33 between binding activities of plasma anti-V2 Abs and anti-gp120 and anti-gp41 Abs, suggesting 34 that deficiency of V2 Abs could be related, in part, to a limited ability to elicit strong Ab 35 responses. Analysis of gp120 sequences revealed that the V2 region of viruses from donors with 36 V2-deficient versus V2-reactive Abs displayed a tendency toward longer length, more glycans, 37 and lower isoelectric point and charge. No differences between these two patient groups were 38 noted in the same parameters measured in the V1 region. These data suggest that immunogens 39 containing a shorter V2 region with fewer glycosylation sites and higher electrostatic charges 40 would be beneficial for induction of anti-V2 Abs, but the ability to mount a strong general Ab 41 response to HIV-1 appears to be a dominant factor. 42IMPORTANCE The results of the RV144 vaccine clinical trial showed a correlation between 43 plasma Abs against a V1V2 fusion protein and a decreased risk of acquiring HIV-1 infection. 44This turned the focus of some HIV vaccine design to the induction of elevated levels of anti-V2 45Abs to increase vaccine efficacy. In plasma samples from Cameroonian individuals infected with 46 HIV-1, we observed broad variations in levels of anti-V2 Abs, and 8 of the 79 plasma samples 47 tested displayed substantial deficiency of V2 Abs. Sequence analysis of the V2 region from 48 plasma viruses and multivariate analyses of V2 characteristics showed a significant difference in 49 several features between V2-deficient and V2-reactive plasma Abs. These results suggest that 50 HIV vaccine immunogens containing a V2 region with shorter length, fewer glycosylation sites, 51 and higher electrostatic charges may be beneficial for induction of a higher level of anti-V2 Abs 52 and thus contribute to HIV vaccine efficacy. 53 54 KEYWORDS HIV-1, V1V2 region, V2 conformational antibodies, V2 linear antibodies, V2 55 antibody deficiency 56 57 4Anti-V2 antibodies (Abs) have been the subject of studies to determine their role in 58 protection against HIV-1 infection due to the results of the Phase III RV144 vaccine trial, which 59 showed an inverse correlation with risk of infection (1). The RV144 data revealed that the V2 60 Abs in vaccinees were highly cross-clade reactive and tha...

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Characterization of neutralizing monoclonal antibodies to linear and conformation-dependent epitopes within the first and second variable domains of human immunodeficiency virus type 1 gp120

Cited by 135 publications

References 58 publications

Comparison of nucleic acid and protein immunization for induction of antibodies specific for HIV-1 gp120

Comparison of nucleic acid and protein immunization for induction of antibodies specific for HIV-1 gp120

Changing Virus‐Host Interactions in the Course of HIV‐1 Infection

Anti-V2 Antibody Deficiency in Individuals Infected With HIV-1

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