Inter‐subtype cross‐neutralizing antibodies recognize epitopes on cell‐associated HIV‐1 virions

Donners, Helen; Davis, David A.; Willems, Betty; Groen, G van der

doi:10.1002/jmv.10288

Cited by 8 publications

(16 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results from the present and previous studies [10], [17], [18] indicate that multiple steps are involved in HIV-1 neutralization so that the virus-antibody complex remains infectious. Antibody binds to the free virion since neutralization increases as the incubation phase is extended.…”

Section: Discussionsupporting

confidence: 68%

Protection in Macaques Immunized with HIV-1 Candidate Vaccines Can Be Predicted Using the Kinetics of Their Neutralizing Antibodies

et al. 2011

Self Cite

View full text Add to dashboard Cite

BackgroundA vaccine is needed to control the spread of human immunodeficiency virus type 1 (HIV-1). An in vitro assay that can predict the protection induced by a vaccine would facilitate the development of such a vaccine. A potential candidate would be an assay to quantify neutralization of HIV-1.Methods and FindingsWe have used sera from rhesus macaques that have been immunized with HIV candidate vaccines and subsequently challenged with simian human immunodeficiency virus (SHIV). We compared neutralization assays with different formats. In experiments with the standardized and validated TZMbl assay, neutralizing antibody titers against homologous SHIVSF162P4 pseudovirus gave a variable correlation with reductions in plasma viremia levels. The target cells used in the assays are not just passive indicators of virus infection but are actively involved in the neutralization process. When replicating virus was used with GHOST cell assays, events during the absorption phase, as well as the incubation phase, determine the level of neutralization. Sera that are associated with protection have properties that are closest to the traditional concept of neutralization: the concentration of antibody present during the absorption phase has no effect on the inactivation rate. In GHOST assays, events during the absorption phase may inactivate a fixed number, rather than a proportion, of virus so that while complete neutralization can be obtained, it can only be found at low doses particularly with isolates that are relatively resistant to neutralization.ConclusionsTwo scenarios have the potential to predict protection by neutralizing antibodies at concentrations that can be induced by vaccination: antibodies that have properties close to the traditional concept of neutralization may protect against a range of challenge doses of neutralization sensitive HIV isolates; a window of opportunity also exists for protection against isolates that are more resistant to neutralization but only at low challenge doses.

show abstract

Section: Discussionsupporting

confidence: 68%

Protection in Macaques Immunized with HIV-1 Candidate Vaccines Can Be Predicted Using the Kinetics of Their Neutralizing Antibodies

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…This index quantifies, by definition, a loss in virus infectivity: it does not matter how much antigen a single infectious dose of virus releases into the culture supernatant as long as this is enough to be registered as significant in an antigen capture ELISA. The culture phase has been extended to 14 days since previous experience has shown that a single infectious dose of virus can be detected after this interval in PBMC cultures even if its replication has been slowed down after exposure to HIV-1 seropositive plasma [Donners et al, 2003a]. In order to detect antibodies binding to the outside of the virion, the incubation phase of the assay has been extended.…”

Section: Discussionmentioning

confidence: 98%

“…The format of a traditional neutralization assay (e.g., 1/2/7) is based on the assumption that antibody binds to a virion when both are suspended in fluid. For primary isolates of HIV, this assumption may not be valid [Spenlehauer et al, 2001;Donners et al, 2003a]. Neutralization with primary HIV isolates may continue, and may only start, after the virus has bound to its target cell.…”

Section: Neutralization With Panel X Plasmamentioning

confidence: 94%

“…Neutralization with primary HIV isolates may continue, and may only start, after the virus has bound to its target cell. From previous studies [Donners et al, 2003a], it would have been expected that the effect of inter-subtype cross-neutralizing antibodies would no longer be detectable after 14 days in culture and yet plasma X1-X3 each neutralize 11 or 12 of 13 sensitive isolates. Therefore, this prediction may not be correct.…”

Section: Neutralization With Panel X Plasmamentioning

confidence: 98%

“…In a previous report from the present laboratory, it was suggested that the antibodies able to neutralize HIV-1 isolates from multiple subtypes recognized epitopes that were exposed when the virions bound to their target cells [Donners et al, 2003a]. The principal contribution to the final neutralization index (the titer of the virus divided by its titer after exposure to antibody) was determined by the absorption phase of the assay.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Epitopes corresponding to the envelope genetic subtype are present on the surface of free virions of HIV‐1 group M primary isolates and can be detected in neutralization assays with extended incubation phases

Davis

Donners

Willems

et al. 2003

Journal of Medical Virology

Self Cite

View full text Add to dashboard Cite

The hypothesis is that there are neutralizing epitopes on the surface of free virions of human immunodeficiency virus type 1 (HIV-1) that correspond to the genetic subtype of the envelope glycoprotein. Assays with extended incubation and reduced absorption phases are required to demonstrate neutralization with antibodies to these epitopes. These assays quantify virus infectivity, rather than reductions in release of antigen into culture supernatants. Neutralizing antibodies reduce virus infectivity by at least 80%, as scored by the presence/absence of antigen released after 14 days in culture of mitogen-transformed peripheral blood mononuclear cells (PBMCs). The epitopes are shared within different subtypes of group M, but not group O, isolates. Individual plasma, selected from three, independent panels of seropositive individuals, cross-neutralize within each subtype as well as the combinations of A with C, B with D or G, and C with CRF01_AE. Isolates within subtype B show the greatest variation in their resistance to neutralization, ranging from highly sensitive to highly resistant. No highly sensitive subtype D isolates were identified. Isolates from subtypes A, C, and CRF01_AE were all resistant. The strategic implication for vaccine design is that antibodies to a limited number of epitopes can neutralize more than 90% of the HIV-1 isolates that are circulating currently in the world. Also, since only antibodies that produce an all-or-nothing loss in virus infectivity can reasonably be expected to prevent the viremic phase after in vivo infection, assays with extended incubation, and culture phases should be used to monitor current efficacy trials.

show abstract

Neutralization kinetics of sensitive and resistant subtype B primary human immunodeficiency virus type 1 isolates

et al. 2006

Self Cite

View full text Add to dashboard Cite

The aim of the study was to determine if sensitive and resistant human immunodeficiency virus type 1 (HIV-1) subtype B primary isolates have different neutralization kinetics. Neutralization assays were undertaken where either the time allowed for virus to react with antibodies or the subsequent period of this mixture's exposure to target cells were varied. The relative neutralization sensitivity/resistance is a reproducible property of the isolates. In a minority of combinations, the titre falls exponentially for as long as the free virions are exposed to antibody. In the remainder, neutralization kinetics shows deviations which may be attributed to events occurring after the virus-antibody mixture is added to the target cells: significant neutralization with minimal exposure of the free virions to antibody; a plot where reduction in virus titre is parallel to the duration of the incubation phase of the assay. Neutralization rate constants are similar for primary HIV-1 SF33, HIV-1 SF162, and HIV-1 89.6, reaching 5 x 10(5)-1 x 10(6)/M sec for the monoclonal antibody IgG1 b12. However, although increased antibody levels produced greater reductions in virus titre the rate of neutralization was not proportional to the antibody concentration. Neutralization of either the free virion or cell-associated virus does not correlate with the resistance/sensitivity of primary subtype B isolates. The target cells play an active role, so that in designing neutralization assays with primary isolates of HIV-1, events following the virus-antibody complex binding to the cell surface have to be taken into consideration.

show abstract

Inter‐subtype cross‐neutralizing antibodies recognize epitopes on cell‐associated HIV‐1 virions

Cited by 8 publications

References 34 publications

Protection in Macaques Immunized with HIV-1 Candidate Vaccines Can Be Predicted Using the Kinetics of Their Neutralizing Antibodies

Protection in Macaques Immunized with HIV-1 Candidate Vaccines Can Be Predicted Using the Kinetics of Their Neutralizing Antibodies

Epitopes corresponding to the envelope genetic subtype are present on the surface of free virions of HIV‐1 group M primary isolates and can be detected in neutralization assays with extended incubation phases

Neutralization kinetics of sensitive and resistant subtype B primary human immunodeficiency virus type 1 isolates

Contact Info

Product

Resources

About