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

The influence of human T-cell leukemia/lymphoma virus type II (HTLV-II) in individuals also infected with HIV-1 is poorly understood. To evaluate the reciprocal influence of HTLV-II and HIV-1 infection, primary peripheral blood mononuclear cell (PBMC) cultures from coinfected individuals were established in the presence of interleukin 2 (IL-2). In these cultures, the kinetics of HTLV-II replication always preceded those of HIV-1. Noteworthy, the kinetics of HIV-1 production were inversely correlated to the HTLV-II proviral load in vivo and its replication ex vivo. These observations suggested a potential interaction between the 2 retroviruses. In this regard, the levels of IL-2, IL-6, and tumor necrosis factor- (TNF-) were measured in the same coinfected PBMC cultures. Endogenous IL-2 was not produced, whereas IL-6 and TNF- were secreted at levels compatible with their known ability to up-regulate HIV-1 expression. The HIV-suppressive CC-chemokines RANTES, macrophage inflammatory protein-1 (MIP-1), and MIP-1β were also determined in IL-2–stimulated PBMC cultures. Of interest, their kinetics and concentrations were inversely related to those of HIV-1 replication. Experiments were performed in which CD8+ T cells or PBMCs from HTLV-II monoinfected individuals were cocultivated with CD4+ T cells from HIV-1 monoinfected individuals separated by a semipermeable membrane in the presence or absence of antichemokine neutralizing antibodies. The results indicate that HTLV-II can interfere with the replicative potential of HIV-1 by up-regulating viral suppressive CC-chemokines and, in particular, MIP-1. This study is the first report indicating that HTLV-II can influence HIV replication, at least in vitro, via up-regulation of HIV-suppressive chemokines.

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ADCC-mediating non-neutralizing antibodies can exert immune pressure in early HIV-1 infection

PLoS Pathogens ◽

10.1371/journal.ppat.1010046 ◽

2021 ◽

Vol 17 (11) ◽

pp. e1010046

Author(s):

Dieter Mielke ◽

Gama Bandawe ◽

Jie Zheng ◽

Jennifer Jones ◽

Melissa-Rose Abrahams ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Immune Escape ◽

Viral Evolution ◽

Neutralizing Antibody ◽

Protective Role ◽

Viral Escape ◽

Immune Pressure ◽

Control Virus ◽

Kinetics Of ◽

Hiv 1

Despite antibody-dependent cellular cytotoxicity (ADCC) responses being implicated in protection from HIV-1 infection, there is limited evidence that they control virus replication. The high mutability of HIV-1 enables the virus to rapidly adapt, and thus evidence of viral escape is a very sensitive approach to demonstrate the importance of this response. To enable us to deconvolute ADCC escape from neutralizing antibody (nAb) escape, we identified individuals soon after infection with detectable ADCC responses, but no nAb responses. We evaluated the kinetics of ADCC and nAb responses, and viral escape, in five recently HIV-1-infected individuals. In one individual we detected viruses that escaped from ADCC responses but were sensitive to nAbs. In the remaining four participants, we did not find evidence of viral evolution exclusively associated with ADCC-mediating non-neutralizing Abs (nnAbs). However, in all individuals escape from nAbs was rapid, occurred at very low titers, and in three of five cases we found evidence of viral escape before detectable nAb responses. These data show that ADCC-mediating nnAbs can drive immune escape in early infection, but that nAbs were far more effective. This suggests that if ADCC responses have a protective role, their impact is limited after systemic virus dissemination.

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Kinetics of Appearance of Neutralizing Antibodies in 12 Patients with Primary or Recent HIV-1 Infection and Relationship with Plasma and Cellular Viral Loads

Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology ◽

10.1097/00042560-199604150-00003 ◽

1996 ◽

Vol 11 (5) ◽

pp. 438-447 ◽

Cited By ~ 44

Author(s):

Isabelle Pellegrin ◽

Elisabeth Legrand ◽

Didier Neau ◽

Pascal Bonot ◽

Bernard Masquelier ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Viral Loads ◽

Kinetics Of ◽

Hiv 1

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Evolutionary Dynamics of the Glycan Shield of theHuman Immunodeficiency Virus Envelope during Natural Infection andImplications for Exposure of the 2G12Epitope

Journal of Virology ◽

10.1128/jvi.78.22.12625-12637.2004 ◽

2004 ◽

Vol 78 (22) ◽

pp. 12625-12637 ◽

Cited By ~ 50

Author(s):

Laurent Dacheux ◽

Alain Moreau ◽

Yasemin Ataman-Önal ◽

François Biron ◽

Bernard Verrier ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Primary Infection ◽

Evolutionary Dynamics ◽

Natural Infection ◽

Virus Envelope ◽

Glycosylation Sites ◽

Immunodeficiency Virus ◽

Kinetics Of ◽

Hiv 1 ◽

2G12 Binding

ABSTRACT Elucidation of the kinetics of exposure of neutralizing epitopes on the envelope of human immunodeficiency virus type 1 (HIV-1) during the course of infection may provide key information about how HIV escapes the immune system or why its envelope is such a poor immunogen to induce broadly efficient neutralizing antibodies. We analyzed the kinetics of exposure of the epitopes corresponding to the broadly neutralizing human monoclonal antibodies immunoglobulin G1b12 (IgG1b12), 2G12, and 2F5 at the quasispecies level during infection. We studied the antigenicity and sequences of 94 full-length envelope clones present during primary infection and at least 4 years later in four HIV-1 clade B-infected patients. No or only minor exposure differences were observed for the 2F5 and IgG1b12 epitopes between the early and late clones. Conversely, the envelope glycoproteins of the HIV-1 quasispecies present during primary infection did not expose the 2G12 neutralizing epitope, unlike those present after several years in three of the four patients. Sequence analysis revealed major differences at potential N-linked glycosylation sites between early and late clones, particularly at positions known to be important for 2G12 binding. Our study, in natural mutants, confirms that the glycosylation sites N295, N332, and N392 are essential for 2G12 binding. This study demonstrates the relationship between the evolving “glycan shield ” of HIV and the kinetics of exposure of the 2G12 epitope during the course of natural infection.

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Neutralizing antibodies inhibit HIV-1 transfer from primary dendritic cells to autologous CD4 T lymphocytes

Blood ◽

10.1182/blood-2012-03-418913 ◽

2012 ◽

Vol 120 (18) ◽

pp. 3708-3717 ◽

Cited By ~ 31

Author(s):

Bin Su ◽

Ke Xu ◽

Alexandre Lederle ◽

Maryse Peressin ◽

Marina Elizabeth Biedma ◽

...

Keyword(s):

Dendritic Cells ◽

T Lymphocytes ◽

Neutralizing Antibodies ◽

Sexual Transmission ◽

Viral Particles ◽

In Trans ◽

In Cis ◽

Kinetics Of ◽

Hiv 1 ◽

Dc Maturation

AbstractDendritic cells (DCs) support only low levels of HIV-1 replication, but have been shown to transfer infectious viral particles highly efficiently to neighboring permissive CD4 T lymphocytes. This mode of cell-to-cell HIV-1 spread may be a predominant mode of infection and dissemination. In the present study, we analyzed the kinetics of fusion, replication, and the ability of HIV-1–specific Abs to inhibit HIV-1 transfer from immature DCs to autologous CD4 T lymphocytes. We found that neutralizing mAbs prevented HIV-1 transfer to CD4 T lymphocytes in trans and in cis, whereas nonneutralizing Abs did not. Neutralizing Abs also significantly decreased HIV-1 replication in DCs, even when added 2 hours after HIV-1 infection. Interestingly, a similar inhibition of HIV-1 replication in DCs was detected with some nonneutralizing Abs and was correlated with DC maturation. We suggest that the binding of HIV-1-specific Abs to FcγRs leads to HIV-1 inhibition in DCs by triggering DC maturation. This efficient inhibition of HIV-1 transfer by Abs highlights the importance of inducing HIV-specific Abs by vaccination directly at the mucosal portal of HIV-1 entry to prevent early dissemination after sexual transmission.

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mRNA Vaccines Induce Rapid Antibody Responses in Mice

10.1101/2021.11.01.466863 ◽

2021 ◽

Author(s):

Makda Gebre ◽

Susanne Rauch ◽

Nicole Roth ◽

Janina Gergen ◽

Jingyou Yu ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Specific Binding ◽

Disease Outbreaks ◽

Antibody Responses ◽

Infectious Disease Outbreaks ◽

Rapid Induction ◽

Kinetics Of ◽

Hiv 1 ◽

Envelope Antigen ◽

Rapid Antibody

mRNA vaccines can be developed and produced quickly, making them attractive for immediate outbreak responses. Furthermore, clinical trials have demonstrated rapid protection following mRNA vaccination. We sought to investigate how quickly mRNA vaccines elicit antibody responses compared to other vaccine modalities. We first examined immune kinetics of mRNA and DNA vaccines expressing SARS-CoV-2 spike in mice. We observed rapid induction of antigen-specific binding and neutralizing antibodies by day 5 following mRNA, but not DNA, immunization. The mRNA vaccine also induced increased levels of IL-5, IL-6 and MCP-1. We then evaluated immune kinetics of an HIV-1 mRNA vaccine in comparison to DNA, protein, and rhesus adenovirus 52 (RhAd52) vaccines with the same HIV-1 envelope antigen in mice. Induction of envelope-specific antibodies was observed by day 5 following mRNA vaccination, whereas antibodies were detected by day 7-14 following DNA, protein, and RhAd52 vaccination. Eliciting rapid humoral immunity may be an advantageous property of mRNA vaccines for controlling infectious disease outbreaks.

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