HIV: The antibodies of 'post-treatment controllers'

Date:
April 14, 2022
Source:
Institut Pasteur
Summary:
A very small percentage of people with HIV-1, known as
'post-treatment controllers' (PTCs), are able to control
their infection after interrupting all antiretroviral
therapy. Understanding the fundamental mechanisms that govern
their immune response is essential in order to develop HIV-1
vaccines, novel therapeutic strategies to achieve remission, or
both. A recent study investigated the humoral immune response --
also known as antibody-mediated immunity -- in some PTCs in whom
transient episodes of viral activity were observed. The researchers
have shown their humoral immune response to be both effective and
robust, which could help to control the infection in the absence
of treatment.



FULL STORY ==========================================================================
A very small percentage of people with HIV-1, known as "post-treatment controllers" (PTCs), are able to control their infection after
interrupting all antiretroviral therapy. Understanding the fundamental mechanisms that govern their immune response is essential in order to
develop HIV-1 vaccines, novel therapeutic strategies to achieve remission,
or both. A recent study investigated the humoral immune response -- also
known as antibody-mediated immunity -- in some PTCs in whom transient
episodes of viral activity were observed. The researchers have shown
their humoral immune response to be both effective and robust, which
could help to control the infection in the absence of treatment.


==========================================================================
The findings of this study, carried out in collaboration with teams
from Institut Pasteur, Inserm and Paris Public Hospitals Group (AP-HP)
and supported by ANRS | Emerging Infectious Diseases and the National Institutes of Health (NIH), were published in Nature Communications on
April 11, 2022.

A very small percentage of people with HIV-1 and who received early
treatment maintained over several years have the capacity to control the
virus over the long-term when their treatment is interrupted. However,
the mechanisms of this control have not been fully elucidated.

The team of researchers, led by Dr. Hugo Mouquet, director of the
Laboratory of Humoral Immunology at Institut Pasteur (partner research organization of Universite' Paris Cite'), conducted an exhaustive
study in PTCs in order to characterize their humoral response
(i.e. their production of B cells and specific antibodies), compared
with non-controllers.

The scientists have shown that the humoral immune response profiles vary according to the activity of the virus observed in the subjects.

In PTCs who experience short episodes in which the virus resumes low-level activity after interruption of treatment, transient exposure to the
viral antigens induces:
* a strong anti-HIV-1 humoral response, involving more frequent
intervention of HIV-1 envelope-specific memory B cells;
* the production of antibodies with a cross-neutralizing action
and which
possess "effector" antiviral activities in which the innate
immune cells recognize the infected cells bound to the antibodies,
thereby inducing their elimination;
* the increase in the blood of atypical memory B cells and
subpopulations
of activated helper T cells.

This specific, multifunctional, and robust humoral response could help
to control their infection in the absence of treatment.

However, other PTCs in whom the virus continuously remains undetectable
after treatment interruption do not develop a strong humoral response. The control mechanisms in these patients continue to be investigated in the VISCONTI study.

The discovery of these two types of humoral immune response, which
depend on the profile of the PTCs, sheds new light on the phenomenon
of HIV control. For Dr. Mouquet, researcher at Institut Pasteur and
principal investigator of the study, "these findings show that early antiretroviral treatment can facilitate the optimal development of
humoral immune responses, in some cases countering viral rebound after treatment interruption." The example of the immune response of the PTCs
having short episodes of "awakening" of the virus could even inspire
novel therapeutic or vaccine strategies.

ANRS VISCONTI: to improve understanding of the HIV control mechanisms
in "post- treatment controllers" The "post-treatment controllers"
whose samples were used for this research are part of the VISCONTI (Viro-Immunological Sustained COntrol after Treatment Interruption)
study, coordinated by Dr. Asier Sa'ez-Cirio'n (Institut Pasteur)
and Dr. Laurent Hocqueloux (Orleans Regional Hospital) and supported
by ANRS for several years. This is the largest cohort of long-term "post-treatment controllers." It includes 30 patients who had received
early treatment that was maintained for several years. Upon interruption
of their antiretroviral therapy, they are able to control their viremia
for a period exceeding 20 years in some cases.

VISCONTI therefore provides the proof of concept of a possible and
sustained state of remission for HIV-1-infected patients. It has paved the
way for the development of novel therapies that target remission from the infection -- if not its eradication. The objective is to enable people
living with HIV-1 to stop their antiretroviral treatment on a lasting
basis, while maintaining viremia at the lowest level and avoiding the
risk of transmission of the virus.


========================================================================== Story Source: Materials provided by Institut_Pasteur. Note: Content may
be edited for style and length.


========================================================================== Journal Reference:
1. Luis M. Molinos-Albert, Vale'rie Lorin, Vale'rie Monceaux,
Sylvie Orr,
Asma Essat, Je're'my Dufloo, Olivier Schwartz, Christine Rouzioux,
Laurence Meyer, Laurent Hocqueloux, Asier Sa'ez-Cirio'n, Hugo
Mouquet, Thierry Prazuck, Barbara De Dieuleveult, Firouze'
Bani-Sadr, Maxime Hentzien, Jean-Luc Berger, Isabelle Kmiec,
Gilles Pichancourt, Safa Nasri, Gilles Hittinger, Ve'ronique
Lambry, Anne-Ce'cile Beauey, Gilles Pialoux, Christia Palacios,
Martin Siguier, Anne Adda, Jane Foucoin, Laurence Weiss,
Marina Karmochkine, Mohamed Meghadecha, Magali Ptak, Dominique
Salmon-Ceron, Philippe Blanche, Marie-Pierre Pie'tri, Jean-
Michel Molina, Olivier Taulera, Caroline Lascoux-Combe, Diane
Ponscarme, Jeannine Delgado Bertaut, Djamila Makhloufi, Matthieu
Godinot, Vale'rie Artizzu, Yazdan Yazdanpanah, Sophie Matheron,
Cindy Godard, Ze'lie Julia, Louis Bernard, Fre'de'ric Bastides,
Olivier Bourgault, Christine Jacomet, Emilie Goncalves, Agne`s
Meybeck, Thomas Huleux, Pauline Cornavin, Yasmine Debab, David
The'ron, Patrick Miailhes, Laurent Cotte, Sophie Pailhes, Stanislas
Ogoudjobi, Jean Paul Viard, Marie-Jose'e Dulucq, Loi"c Bodard,
Francoise Churaqui, Thomas Guimard, Laetitia Laine. Transient viral
exposure drives functionally-coordinated humoral immune responses
in HIV-1 post-treatment controllers. Nature Communications, 2022;
13 (1) DOI: 10.1038/s41467-022-29511-1 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220414110753.htm

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