Prospects for Prevention of and Early Intervention Against HIV

Bolognesi, Dani P.

doi:10.1001/jama.1989.03420200097045

Cited by 28 publications

(10 citation statements)

References 68 publications

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“…DISCUSSION A globally effective HIV-1 vaccine should be able to counter all subtypes of HIV-1, not just locally circulating variants related genetically to the immunogen. The variation of HIV-1 within an individual, between individuals, and between strains circulating in different parts of the world has always been a major obstacle to vaccine design (7,28,30,31,54,70). For example, the current subunit gp120 or gp160 vaccine candidates are of a fixed genetic composition, and so there has been a concern about the breadth, as well as the potency, of the humoral immune responses that they are able to generate (24,38,81).…”

Section: Fig 2 Binding Of Cd4-igg2 Andmentioning

confidence: 99%

“…For example, the current subunit gp120 or gp160 vaccine candidates are of a fixed genetic composition, and so there has been a concern about the breadth, as well as the potency, of the humoral immune responses that they are able to generate (24,38,81). Thus, it has been considered that cocktails of immunogens might be necessary to counter HIV-1 diversity or that vaccines might need to be tailored to match the predominant, locally circulating strains in each geographic area (7).…”

Section: Fig 2 Binding Of Cd4-igg2 Andmentioning

confidence: 99%

“…Up until recently, the major focus of HIV-1 neutralization studies has been the V3 loop of gp120, as this region contains the principal neutralizing determinant (PND) for T-cell lineadapted strains such as HIV-1 LAI and HIV-1 MN (27). Overcoming the variation in V3 sequences has, therefore, been at the forefront of vaccine design strategies (7,15,50,62,63). However, it is now widely accepted that adaptation of primary isolates to growth in T-cell lines selects for variants that are abnormally neutralization sensitive, not only to HIV-1-positive sera but also to soluble CD4 and to MAbs against a wide range of gp120 or gp41 epitopes (3,38,40,43,45,47,59,71,73,77,81).…”

Section: Fig 2 Binding Of Cd4-igg2 Andmentioning

confidence: 99%

“…Furthermore, the correlates of protective immunity to field isolates of HIV-1 remain unknown, complicating rational vaccine design. However, it remains logical to assume that the induction of broadly neutralizing antibodies is a desirable feature of a vaccine candidate, on the grounds that preexisting antibodies may prevent the transmis-sion of cell-free HIV-1 or limit the initial dissemination of a transmitted infection (7).…”

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confidence: 99%

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Cross-clade neutralization of primary isolates of human immunodeficiency virus type 1 by human monoclonal antibodies and tetrameric CD4-IgG

Trkola

Pomales

Yuan

et al. 1995

J Virol

453

157

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We have tested three human monoclonal antibodies (MAbs) IgG1b12, 2G12, and 2F5) to the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1), and a tetrameric CD4-IgG molecule (CD4-IgG2), for the ability to neutralize primary HIV-1 isolates from the genetic clades A through F and from group O. Each of the reagents broadly and potently neutralized B-clade isolates. The 2F5 MAb and the CD4-IgG2 molecule also neutralized strains from outside the B clade, with the same breadth and potency that they showed against B-clade strains. The other two MAbs were able to neutralize a significant proportion of strains from outside the B clade, although there was a reduction in their efficacy compared with their activity against B-clade isolates. Neutralization of isolates by 2F5 correlated with their possession of the LDKW motif in a segment of gp41 near the membrane-spanning domain. The other two MAbs and CD4-IgG2 recognize discontinuous binding sites on gp120, and so no comparison between genetic sequence and virus neutralization was possible. Our data show that a vaccine based on the induction of humoral immunity that is broadly active across the genetic clades is not impossible if immunogens that express the epitopes for MAbs such as 2F5, 2G12, and IgG1b12 in immunogenic configurations can be created. Furthermore, if the three MAbs and CD4-IgG2 produce clinical benefit in immunotherapeutic trials in the United States or Europe, they may also do so elsewhere in the world.

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Section: Fig 2 Binding Of Cd4-igg2 Andmentioning

confidence: 99%

Section: Fig 2 Binding Of Cd4-igg2 Andmentioning

confidence: 99%

Section: Fig 2 Binding Of Cd4-igg2 Andmentioning

confidence: 99%

mentioning

confidence: 99%

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Cross-clade neutralization of primary isolates of human immunodeficiency virus type 1 by human monoclonal antibodies and tetrameric CD4-IgG

Trkola

Pomales

Yuan

et al. 1995

J Virol

453

157

View full text Add to dashboard Cite

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“…It has been known for almost a decade that human immunodeficiency virus type 1 (HIV-1) can be neutralized by antibodies directed at its envelope glycoproteins (29,61,74). The observations of virus neutralization in vitro by sera from naturally infected humans and by human or animal antisera to recombinant forms of the gp120 glycoprotein, or fragments thereof (5,11,22,26,30,31,36,38,59,62,64,70), underlie much of the reasoning that humans might be successfully immunized against HIV-1 by subunit vaccines (6,18,27,39), although the importance of cellular immunity in controlling HIV-1 infection should not be underestimated (33). However, until recently, neutralization assays have generally relied on the use of HIV-1 strains adapted to growth in transformed T-cell lines, as these viruses can be grown conveniently to high titers.…”

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confidence: 99%

Primary isolates of human immunodeficiency virus type 1 are relatively resistant to neutralization by monoclonal antibodies to gp120, and their neutralization is not predicted by studies with monomeric gp120

Moore

Cao

Qing

et al. 1995

J Virol

376

153

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A panel of anti-gp120 human monoclonal antibodies (HuMAbs), CD4-IgG, and sera from people infected with human immunodeficiency virus type 1 (HIV-1) was tested for neutralization of nine primary HIV-1 isolates, one molecularly cloned primary strain (JR-CSF), and two strains (IIIB and MN) adapted for growth in transformed T-cell lines. All the viruses were grown in mitogen-stimulated peripheral blood mononuclear cells and were tested for their ability to infect these cells in the presence and absence of the reagents mentioned above. In general, the primary isolates were relatively resistant to neutralization by the MAbs tested, compared with the T-cell line-adapted strains. However, one HuMAb, IgG1b12, was able to neutralize most of the primary isolates at concentrations of Յ1 g/ml. Usually, the inability of a HuMAb to neutralize a primary isolate was not due merely to the absence of the antibody epitope from the virus; the majority of the HuMAbs bound with high affinity to monomeric gp120 molecules derived from various strains but neutralized the viruses inefficiently. We infer therefore that the mechanism of resistance of primary isolates to most neutralizing antibodies is complex, and we suggest that it involves an inaccessibility of antibody binding sites in the context of the native glycoprotein complex on the virion. Such a mechanism would parallel that which was previously postulated for soluble CD4 resistance. We conclude that studies of HIV-1 neutralization that rely on strains adapted to growth in transformed T-cell lines yield the misleading impression that HIV-1 is readily neutralized. The more relevant primary HIV-1 isolates are relatively resistant to neutralization, although these isolates can be potently neutralized by a subset of human polyclonal or monoclonal antibodies.

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Current status of clinical laboratory tests for the human immunodeficiency virus

Nakamura

Bylund

Rooney³

1990

Clinical Laboratory Analysis

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The predictive values of positive and negative test results for human immunodeficiency virus (HIV) antibody are extremely high in laboratories that have good quality control and high performance standards and use licensed FDA-approved enzyme immunoassay (EIA) and Western blot standardized tests. With a carefully designed protocol, the false-positive rate of combined EIA and Western blot has been reported to be as low as 1 in 10(5). When results of HIV confirmatory antibody tests are indeterminate, other tests such as culture and nucleotide probe methods for HIV DNA or RNA may help resolve false-reactive screening EIA tests. Improvements are constantly in progress for HIV laboratory tests with the use of recombinant DNA-derived antigens and synthetic polypeptides. With the use of new-generation synthetic polypeptide antigens, specific assays to identify HIV-1 and HIV-2 have been developed. Recently, assays for the HIV regulatory gene products have been studied for their predictive potential. Antibodies to nef protein, a regulator of HIV-1 replication, may be an early indicator of HIV infection.

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Prospects for Prevention of and Early Intervention Against HIV

Cited by 28 publications

References 68 publications

Cross-clade neutralization of primary isolates of human immunodeficiency virus type 1 by human monoclonal antibodies and tetrameric CD4-IgG

Cross-clade neutralization of primary isolates of human immunodeficiency virus type 1 by human monoclonal antibodies and tetrameric CD4-IgG

Primary isolates of human immunodeficiency virus type 1 are relatively resistant to neutralization by monoclonal antibodies to gp120, and their neutralization is not predicted by studies with monomeric gp120

Current status of clinical laboratory tests for the human immunodeficiency virus

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