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Preclinical Tests Show Antibody Stops Covid-19 Variants

Human B-cell

Human B-cell (NIAID, Flickr)

13 Apr. 2022. Lab studies show an experimental synthetic antibody protects animals and neutralizes all SARS-CoV-2 variants of concern, including omicron BA.2. A team from Institut Pasteur in Paris describes the findings on the bioRxiv pre-print server, published 1 April, in advance of peer-review and journal publication.

Highly targeted synthetic antibodies, known as monoclonal antibodies, are among the leading therapies for treating Covid-19 infections. Recent research results, however, indicate some monoclonal antibodies designed to act on the original SARS-CoV-2 viral strain or early variants, are less effective in treating infections from newer variants becoming more prevalent. Findings from a study of blood sample tests published last month in the journal Nature Medicine show some current monoclonal antibodies working alone or in antibody cocktails neutralize earlier variants, but have limited or no effect on more recent omicron BA.1 or BA.2 variants. According to Centers for Disease Control and Prevention, the more contagious BA.2 variant is responsible for 86 percent of new Covid-19 infections, with omicron BA.1 responsible for another 13 percent, in the week ending 9 April.

Immunologist Hugo Mourquet and lab colleagues at Institut Pasteur study molecular reactions of B-cells, white blood cells  in the immune system that produce antibodies in response to invading pathogens, also known as humoral immunity. Mourquet’s lab studies B-cell responses to a range of infectious diseases, including SARS-CoV-2. In 2021, Mourquet and venture investor Truffle Capital in Paris, formed the company SpikImm to develop a synthetic antibody code-named SPK001 to prevent and treat Covid-19 infections, including a broad range of variants. SPK001 is designed particularly for people with compromised immune systems, such as transplant patients and people with blood-related cancers or autoimmune disorders.

Reduced SARS-CoV-2 in lungs

In their paper, Mourquet’s team screened 102 monoclonal antibodies that target the SARS-CoV-2 coronavirus spike protein in blood samples from 10 people with compromised immune systems. Among the most potent antibodies to emerge from the screening are two specific immunoglobulin G and A antibodies that neutralize the original SARS-CoV-2 strain, as well as variants alpha, beta, gamma, delta, and omicron BA.1 and BA.2. Of those two candidates, say the authors, the immunoglobulin G or IgG antibody shows the most promise in its chemical structure and activity against the full range of variants.

The researchers tested the IgG antibody first in lab mice as a treatment for Covid-19 infections. Mice infected with the original Covid-19 virus and treated with the immunoglobulin G antibody survive after a temporary weight loss, while non-treated mice lose about 25 percent of their body weight in six days. In another test, infected hamsters treated with the IgG antibody, show reduced SARS-CoV-2 infections and RNA levels in their lungs compared to hamsters given non-therapeutic antibodies. In a third set of tests, researchers found the IgG antibody protects lab mice from infections caused by the SARS-CoV-2 beta variant, with the antibodies remaining in blood samples after a follow-up period.

The IgG antibody is licensed to SpikImm for development as SPK001 to prevent Covid-19 infections among people with compromised immune systems. “SPK001 was selected among hundreds of screened anti-SARS-CoV-2 monoclonals,” says Mourquet in a Truffle Capital statement released through BusinessWire, “and cross-neutralizes all SARS-CoV-2 variants of concern including delta, omicron BA.1 and BA.2. With its breadth and potency, documented by strong structural data, SPK001 appears as a prime candidate for Covid-19 prevention in immunocompromised patients.”

SpikImm says a clinical trial of SPK001 is planned in mid-2022 and later in a mid-stage trial with immunocompromised patients.

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