SARS-CoV-2: Neutralization of BA.1 and BA.2 by therapeutic monoclonal antibodies

Date:
April 11, 2022
Source:
Institut Pasteur
Summary:
Scientists studied the sensitivity of Omicron BA.1 and BA.2 to
nine monoclonal antibodies, some of which are used in pre-exposure
prophylaxis in immunocompromised individuals. The scientists showed
a loss of neutralizing activity against BA.1 and BA.2 in people
treated with two antibody cocktails.



FULL STORY ==========================================================================
The SARS-CoV-2 Omicron BA.1 sublineage has been supplanted in many
countries by the BA.2 sublineage. Although Omicron is responsible for less severe forms in the general population, immunocompromised people are still
at higher risk of developing severe forms of COVID-19. Several monoclonal antibodies are currently available in clinical practice as a preventive treatment for these patients. Scientists from the Institut Pasteur, the
CNRS, the Vaccine Research Institute (VRI), in collaboration with Orle'ans Regional Hospital, the Paris Public Hospital Network (AP-HP), KU Leuven
(the Catholic University of Leuven) and Universite' Paris Cite', studied
the sensitivity of Omicron BA.1 and BA.2 to nine monoclonal antibodies,
some of which are used in pre-exposure prophylaxis in immunocompromised individuals. The scientists showed a loss of neutralizing activity
against BA.1 and BA.2 in people treated with two antibody cocktails (Ronapreve(R) or Evusheld(R)). These findings were published in Nature
Medicine on March 23, 2022.


==========================================================================
The Omicron sublineage BA.2 has become increasingly common and is now
dominant in several countries, including France. Scientists from the
Institut Pasteur's Virus and Immunity Unit (a joint research unit with
the CNRS) and the VRI began by studying the sensitivity of the Omicron
BA.1 and BA.2 sublineages to therapeutic monoclonal antibodies in a
cell culture system. This step involved isolating an infectious BA.2
strain in collaboration with the Rega Institute at KU Leuven. They then examined the efficacy of pre-exposure prophylaxis in immunocompromised individuals at risk of developing severe COVID-19. The scientists
first described the in vitro sensitivity of BA.2 to nine therapeutic antibodies, as compared to the Delta variant and Omicron BA.1. They
went on to examine the clinical implications of these observations by
measuring the neutralizing activity of the antibodies in sera from 29 individuals who had been treated with Ronapreve(R) (a cocktail of two antibodies developed by Roche/Regeneron) and/or Evusheld(R) (a cocktail
of two antibodies developed by AstraZeneca).

The scientists compared the ability of the patients' sera to tackle
BA.1 and BA.2 between 3 and 30 days after treatment. The results of
the study show that therapeutic sensitivity varies depending on the
Omicron sublineage.

"We show that the antibodies and corresponding sera are inactive or only
weakly active against BA.1, but more active against BA.2. As compared
to the Delta variant, neutralizing titers were more markedly decreased
against BA.1 (344- fold) than BA.2 (9-fold)," explained Timothe'e Bruel,
lead author of the study and a scientist in the Virus and Immunity Unit
at the Institut Pasteur (a joint research unit with the CNRS) with regard
to Evusheld(R).

Four Omicron infections were also reported among the 29 patients treated
with antibodies (including one severe case). "This shows that, in this
case, treatment does not fully protect against infection or against severe forms," explained Thierry Prazuck, co-last author of the study and Head
of the Infectious Diseases Department at Orle'ans Regional Hospital.

"To our knowledge, this is the first study to directly describe
the seroneutralization of individuals treated with monoclonal
antibodies against Delta, BA.1 and BA.2, and to link the results with infections. BA.1, and to a lesser extent BA.2, is less sensitive to
Evusheld(R) and Ronapreve(R) than Delta. This suggests that these
treatments are probably less clinically effective against Omicron
infection than against Delta," commented Olivier Schwartz, last author of
the study and Head of the Virus and Immunity Unit at the Institut Pasteur
(a joint research unit with the CNRS).

There are thought to be 230,000 immunocompromised people in France,
including individuals receiving immunosuppressants for a transplant or chemotherapy for cancer, patients with autoimmune diseases and those yet
to be treated for HIV infection. The antibodies have been administered
to tens of thousands of individuals worldwide. This therefore represents
a major public health issue which will require further clinical studies
so that treatments can be adjusted in line with circulating variants.


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


========================================================================== Journal Reference:
1. Timothe'e Bruel, Je'ro^me Hadjadj, Piet Maes, Delphine Planas,
Aymeric
Seve, Isabelle Staropoli, Florence Guivel-Benhassine, Franc,oise
Porrot, William-Henry Bolland, Yann Nguyen, Marion Casadevall,
Caroline Charre, He'le`ne Pe're', David Veyer, Matthieu Prot, Artem
Baidaliuk, Lize Cuypers, Cyril Planchais, Hugo Mouquet, Guy Baele,
Luc Mouthon, Laurent Hocqueloux, Etienne Simon-Loriere, Emmanuel
Andre', Benjamin Terrier, Thierry Prazuck, Olivier Schwartz. Serum
neutralization of SARS-CoV- 2 Omicron sublineages BA.1 and BA.2 in
patients receiving monoclonal antibodies. Nature Medicine, 2022;
DOI: 10.1038/s41591-022-01792-5 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220411101316.htm

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