CD4 as A Target for SARS-CoV-2 Antibody Development

The pneumonia outbreak in Wuhan of China is derived from a novel coronavirus, SARS-CoV-2, named by the International Committee on Taxonomy of Viruses (ICTV). This infection is spreading widely around China and other countries. However, there are no specific, antiviral treatments for SARS-CoV-2 at the time of the outbreaks beyond home quarantine and supportive measures.

With advanced platforms and dedicated devices in antibody development and manufacturing, Creative Biolabs has noticed that neutralizing antibodies (nAbs) are a prominent specific defense against viral infections. In the case of SARS-CoV-2, our teams are already trying existing antivirals, such as anti-HIV drugs, and offer custom antibody development services for effective nAbs, to see whether they have activity against this new virus.

• Cluster of Differentiation 4 (CD4) & HIV

HIV is an abbreviation of the human immunodeficiency virus that can damage the immune system of the body. There’re two classes of HIV, including HIV-1 and HIV-2. A person with HIV can develop acquired immunodeficiency syndrome (AIDS), a chronic, life-threatening opportunistic infection without treatment. HIV attacks the immune system because it targets CD4+ T cells. The virus grabs on to the surface of a cell, gets inside, and fuses to a part of it. Once the infected CD4 cell dies, it will release a lot of copies of HIV viruses into the bloodstream. In the last year, some reviews underlined the abundant new knowledge gained from studies on HIV-infected individuals with broadly nAbs (bnAbs) and contemplated on how such results might inform drug design. It is widely accepted that one of the four major sites of vulnerability on the HIV-1 envelope glycoproteins is the CD4 binding site (CD4bs).

• Recent Findings

In 2014, the Food and Drug Administration (FDA) approves Ibalizumab (TMB-355) manufactured in several pharmaceutical companies. Ibalizumab is a monoclonal antibody (mAb) and functions as a viral entry inhibitor in the HIV/AIDS infection. It is different from other viral-entry inhibitors since it binds to the CD4 molecule and interferes with virus penetration into cells. This mAb is the first virus entry blocker in the treatment of HIV/AIDS and is currently developing a subcutaneous injection delivery system after a successful Phase IIb trial.

• Anti-CD4 Antibody Development for SARS-CoV-2

Fig.2 Overall steps in development of specific immunity. (Payne, 2018)

When a frightening virus emerges in humans, much time and money would be spent to develop and test a new drug or vaccine. Finding new therapeutics also takes a long time, but there is another option to have a try on existing drugs. Antibody-mediated neutralization of viruses is the direct inhibition of viral infectivity resulting from antibody docking to virus particles. When it comes to SARS-CoV-2, Creative Biolabs outlines different potential treatments that may be pursued as a therapy for SARS-CoV-2 and is focusing on antivirals broadly used to treat HIV, hoping they could fight the coronavirus as well.

Ibalizumab, as a nAb, is an important component of licensed antiviral vaccines. Despite intensive efforts, attempts to create an HIV-1 vaccine that evokes protective antibody responses still failed. Nabs in natural HIV-1 infection confront with rapid virus escape and primarily target the autologous virus with limited cross-neutralization activity. In the past decade, the discovery of bnAbs that neutralize almost all HIV-1 strains across varying subtypes has revitalized HIV-1 vaccine development. Furthermore, bnAb treatment for HIV-1 has indicated the capacity to delay rebound during analytic treatment interruption, to reduce viremia and virus set points in a great number of individuals. These capacities emphasized prospects for bnAb-based therapies. Particularly, bnAbs, preventing infection in animal models by mucosal issues, lay a solid foundation for bnAb-based vaccines.

As a top-ranking supplier in the recombinant antibody market, Creative Biolabs pays attention to current knowledge of the determinants of bnAb induction with a specific emphasis on SARS-CoV-2 and provides one-stop services to assist customers in developing high-quality antibody medicines directing CD4 target. Other still experimental antivirals, including one that has been unsuccessfully tested for Ebola, may also hold promise by our experts to engineer in the future. For more information on the development of antibody drugs, please directly contact us or consult our technical supports online.

Reference

1. Payne, S. Immunity and Resistance to Viruses. Viruses. 2018, Chaper6: 62-70.

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