Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell–free virions from blood plasma

Igarashi, Tatsuhiko; Brown, Charles R.; Azadegan, A A; Haigwood, Nancy L.; Dimitrov, Dimiter S.; Martin, Malcolm A.; Shibata, Riri

doi:10.1038/5576

Cited by 161 publications

(130 citation statements)

References 22 publications

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“…Moreover, their importance in the early control of HIV-1 infection is implied by the finding of immune complexes containing HIV-1 RNA (Dianzani et al 2002), which could be an explanation for the disparity between quantification of viral RNA and of infectious HIV virions (Igarashi et al 1999). Also, the increase in neutralization susceptibility of cultured HIV-1 and its decrease after inoculation indirectly confirms the control displayed by HIV-1 neutralizing antibodies in infection (Pugach et al 2004).…”

Section: Discussionmentioning

confidence: 68%

Human immunodeficiency virus type 1 neutralization by plasma from B or F genotype infected individuals

Bongertz

Teixeira

Grinztejn

et al. 2005

Mem. Inst. Oswaldo Cruz

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Anti-human immunodeficiency virus type 1 (HIV-1) "binding antibodies" (antibodies capable of binding to synthetic peptides or proteins) occur throughout HIV-1 infection, are high-titered and highly cross-reactive, as confirmed in this study by analyzing plasma from B and F genotype HIV-1 infected individuals. Plasma from individuals infected with clade F HIV-1 displayed the most frequent cross-reactivity, in high titers, while Bbr plasma showed much higher specificity. Similarly, neutralization of a reference HIV-1 isolate (HIV-1 MN) was more frequently observed by plasma from F than B genotype infected individuals. No significant difference was seen in neutralization susceptibility of primary B, Bbr or F clade HIV-1 by plasma from individuals infected with the classical B (GPGR) or F HIV-1, but Bbr (GWGR) plasma were less likely to neutralize the F genotype primary HIV-1 isolates. The data indicate that both B and F genotype derived vaccines would be equally effective against B and F HIV-1 infection, with a slightly more probable effectiveness for F than B genotype. Although the Bbr variant appears to induce a much more specific humoral immune response, the susceptibility in neutralizing the Brazilian HIV-1 B genotype Bbr variant is similar to that observed with the classical B genotype HIV-1

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Section: Discussionmentioning

confidence: 68%

Human immunodeficiency virus type 1 neutralization by plasma from B or F genotype infected individuals

Bongertz

Teixeira

Grinztejn

et al. 2005

Mem. Inst. Oswaldo Cruz

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“…The approach used in our investigation is noteworthy in that a potent neutralizing highaffinity antibody against an emerging pathogen was readily selected from nonimmune human antibody library. Passive immunization has been proven to be an effective and safe strategy for the prevention and treatment of viral disease (22)(23)(24)(25). The passive administration of neutralizing human monoclonal antibodies could provide an immediate treatment strategy for emergency prophylaxis and treatment of SARS, while the alternative and more time-consuming development of vaccines and new drugs is underway.…”

Section: Resultsmentioning

confidence: 99%

Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association

Sui

Murakami

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

567

603

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Effective prophylaxis and antiviral therapies are urgently needed in the event of reemergence of the highly contagious and often fatal severe acute respiratory syndrome (SARS) coronavirus (SARSCoV) infection. We have identified eight recombinant human single-chain variable region fragments (scFvs) against the S1 domain of spike (S) protein of the SARS-CoV from two nonimmune human antibody libraries. One scFv 80R efficiently neutralized SARS-CoV and inhibited syncytia formation between cells expressing the S protein and those expressing the SARS-CoV receptor angiotensin-converting enzyme 2 (ACE2). Mapping of the 80R epitope showed it is located within the N-terminal 261-672 amino acids of S protein and is not glycosylation-dependent. 80R scFv competed with soluble ACE2 for association with the S1 domain and bound S1 with high affinity (equilibrium dissociation constant, K d ‫؍‬ 32.3 nM). A human IgG1 form of 80R bound S1 with a 20-fold higher affinity of 1.59 nM comparable to that of ACE2 (K d ‫؍‬ 1.70 nM), and neutralized virus 20-fold more efficiently than the 80R scFv. These data suggest that the 80R human monoclonal antibody may be a useful viral entry inhibitor for the emergency prophylaxis and treatment of SARS, and that the ACE2-binding site of S1 could be an attractive target for subunit vaccine and drug development.T he severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV), a newly emergent member in the family Coronaviridae, causes SARS for which there are no vaccines or effective therapies currently available (1-4). It has been reported that high titers of protecting IgG antibody to SARS-CoV are present in convalescent serum, and SARS patients show clinical improvement if they are given serum from previously infected patients (5, 6). These observations suggest that passive immunization with human monoclonal antibodies could be developed for the treatment of SARS (7). The spike (S) proteins of coronaviruses are large type-I transmembrane glycoproteins that are responsible for receptor binding and membrane fusion. Two functional domains at the amino (S1) and carboxy (S2) termini of the S protein are conserved among the coronaviruses. The S1 and S2 domain of SARS-CoV S protein can be identified by sequence alignment with other coronavirus S proteins, especially with the more conserved S2 domain (8-10). The S protein is also the major antigenic determinant for coronaviruses (9,(11)(12)(13)(14). It has recently been demonstrated that the binding of the S1 domain to its receptor angiotensinconverting enzyme 2 (ACE2) on host cells is responsible for SARS-CoV entry into cells (15). Therefore, we targeted the S1 protein for generation of neutralizing human monoclonal antibodies. Here we report the identification, production, and characterization of a neutralizing human monoclonal antibody 80R against SARS-CoV that blocks the binding of S1 to ACE2. Materials and MethodsExpression and Purification of SARS-CoV S1 and Truncated S1. Plasmids encoding SARS-CoV S protein residues 12-672, 12-327, o...

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“…Assuming HIV virions are produced by piCD4s at the rate k 19 · piCD4 and are phagocytosed by phagocyes at the rate k 20 · V, we obtain (8) Consequently, the model of HIV infection without mutation is given by Eqs. 1 8.…”

Section: Modelingmentioning

confidence: 99%

“…nisms that seem to be involved in HIV infection, e.g., HIV-specific helper T cells, anti-HIV antibodies, macrophages, dendritic cells, chemokines, viral tropism (T-cell-line-tropic or macrophage-tropic), viral mutation causing drug resistance, opportunistic infections and neoplasms (1,2,11,12,19,23,31,35,37).…”

mentioning

confidence: 99%

Computer Simulations of Slow Progression of Human Immunodeficiency Virus Infection and Relapse during Anti‐HIV Treatment with Reverse Transcriptase Inhibitors and Protease Inhibitors

Takahashi

Ohuchi

2002

Microbiology and Immunology

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Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) have been serious problems since the 1980s. Although the progression of HIV infection into AIDS can be controlled well with the use of reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs) (40), the long-term efficacy of such treatment is not known. Furthermore, since recent clinical data have suggested that the dynamics of HIV infection is more complex than had been thought, more studies on HIV are required.Since we consider it important to understand the interactions among HIV, immunity and anti-HIV drugs, we propose new mathematical models of HIV infection. In modeling HIV infection, we paid attention to the following facts: 1) lymphoid organs are major reservoirs for HIV virions (13, 18, 26 28, 39), 2) the viral load in lymphoid organs does not necessarily correspond with that in blood (28, 39), 3) lymphoid organs contain 98% of the total lymphocyte pool (25,36,45), 4) changes in the lymphocyte count and the CD4/CD8 ratio in lymphoid organs do not necessarily correspond with those in blood (25, 36), and 5) relations between stimuli and responses are nonlinear (9, 20). Thus we assumed that the interactions occur in lymphoid organs. We also defined a function to calculate the nonlinear relations.In this study, we present three models of HIV infecMicrobiol. Immunol., 46(6), 397 407, 2002 397Abbreviations: AIDS, acquired immunodeficiency syndrome; CTL, cytotoxic T lymphocyte; HIV, human immunodeficiency virus; liCD4, latently infected CD4 T cell; niCD4, non-infected CD4 T cell; npiCD4, non-productively infected CD4 T cell; PI, protease inhibitor; piCD4, productively infected CD4 T cell; RTI, reverse transcriptase inhibitor. Abstract: Human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) have been very serious problems since the 1980s. The progression of HIV infection into AIDS can be suppressed to some extent with reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs); however, there are some serious problems with treatments using the anti-HIV drugs (e.g. very high expense, complicated administration, and drug resistance). Hence, more studies on HIV and the development of more effective anti-HIV treatments are required. We consider it important to understand the complex dynamics involved in HIV infection, and we therefore propose new mathematical models of HIV infection. In the modeling, we have paid attention to the nonlinear relations between stimuli and responses (i.e., when responses are plotted against the logarithm of stimuli, a sigmoid curve is obtained), and to lymphoid organs which seem more important than the blood compartment (i.e., lymphoid organs are major reservoirs of HIV virions and contain most of the lymphocytes). Using the models, we have found that viral antigenic mutation plays an important role in the slow progression in the chronic phase of HIV infection. We have also found that viral antigenic mutation can cause relapse of HIV in...

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Human immunodeficiency virus type 1 neutralizing antibodies accelerate clearance of cell–free virions from blood plasma

Cited by 161 publications

References 22 publications

Human immunodeficiency virus type 1 neutralization by plasma from B or F genotype infected individuals

Human immunodeficiency virus type 1 neutralization by plasma from B or F genotype infected individuals

Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association

Computer Simulations of Slow Progression of Human Immunodeficiency Virus Infection and Relapse during Anti‐HIV Treatment with Reverse Transcriptase Inhibitors and Protease Inhibitors

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