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Review
. 2021 Apr 22;20(1):88.
doi: 10.1186/s12934-021-01576-5.

Integrative overview of antibodies against SARS-CoV-2 and their possible applications in COVID-19 prophylaxis and treatment

Norma A Valdez-Cruz  1 , Enrique García-Hernández  2 , Clara Espitia  3 , Laura Cobos-Marín  4 , Claudia Altamirano  5 , Carlos G Bando-Campos  6 , Luis F Cofas-Vargas  2 , Enrique W Coronado-Aceves  3 , Ricardo A González-Hernández  6 , Pablo Hernández-Peralta  4 , Daniel Juárez-López  6 , Paola A Ortega-Portilla  3 , Sara Restrepo-Pineda  6 , Patricio Zelada-Cordero  6 , Mauricio A Trujillo-Roldán  7
Affiliations
Review

Integrative overview of antibodies against SARS-CoV-2 and their possible applications in COVID-19 prophylaxis and treatment

Norma A Valdez-Cruz et al. Microb Cell Fact. .

Abstract

SARS-CoV-2 is a novel β-coronavirus that caused the COVID-19 pandemic disease, which spread rapidly, infecting more than 134 million people, and killing almost 2.9 million thus far. Based on the urgent need for therapeutic and prophylactic strategies, the identification and characterization of antibodies has been accelerated, since they have been fundamental in treating other viral diseases. Here, we summarized in an integrative manner the present understanding of the immune response and physiopathology caused by SARS-CoV-2, including the activation of the humoral immune response in SARS-CoV-2 infection and therefore, the synthesis of antibodies. Furthermore, we also discussed about the antibodies that can be generated in COVID-19 convalescent sera and their associated clinical studies, including a detailed characterization of a variety of human antibodies and identification of antibodies from other sources, which have powerful neutralizing capacities. Accordingly, the development of effective treatments to mitigate COVID-19 is expected. Finally, we reviewed the challenges faced in producing potential therapeutic antibodies and nanobodies by cell factories at an industrial level while ensuring their quality, efficacy, and safety.

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Conflict of interest statement

Authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Mechanisms in adverse and protective immune response for SARS-CoV-2. Upper panel (red). Adverse immune response in the presence of SARS-CoV-2 include mechanisms like complement hyperactivation and hypercoagulable state, excessive macrophage migration, macrophage activation syndrome, NK exhaustion, insufficient antigen presentation, exhausted CD4+ and CD8+ T cell and antibody-dependent enhancement (ADE) *This response has been described by in vitro models. Lower panel (blue). Protective immune response is characterized by complement system activation trough IgM natural antibodies (** this has been suggested as an initial barrier for SARS-CoV-2 infection), TLRs activation, NK and T cell normal activation and antibody virus neutralization by B cells. APC antigen presenting cell, ER endoplasmic reticulum, FcgRII receptor II for the Fc region of immunoglobulin G, GM-CSF Granulocyte–macrophage colony-stimulating factor, MAC membrane attack complex, MBL mannan-binding lectin, MHC major histocompatibility complex, MSP mannose-associated serine proteases, Nab neutralizing antibody, TCR T-cell receptor, TLR Toll-like receptor
Fig. 2
Fig. 2
Diagram of antibodies and their respective fragments, from sources such as human, mouse, genetically humanized mouse, and alpaca. a mAb general view fragment antigen-binding region composed of two heavy and two light chains, disposed in Fab fragment and the fragment crystallizable (Fc) which consists of constant heavy chains (CH2 and CH3). The variable region formed by two arms which bind to antigen through complementary determining regions (CDRs). b Fab fragment is formed by the light chain (VL and CL) and by the heavy chain’s variable (VH) region and a portion of its constant (CH1). c A single-chain variable fragment (scFv) comprises the fusion of the VH and VL of immunoglobulins, connected by a linker peptide. d Single domain antibody (nanobody) consists of a monomeric variable domain (VH) of a heavy-chain antibody of a common IgG. e Antibodies from Camelidae or heavy-chain antibodies, presenting a variable region of a heavy chain (VHH) and do not present light chains. f The VHH (Nanobody) derived from heavy-chain only antibodies have a longer CDR3 loop compared to VH-VL domains in mAbs
Fig. 3
Fig. 3
Methods of extraction and administration of Convalescent Plasma (CP). a a convalescent donor who has developed antibodies after recovering from the disease could donate plasma (usually through plasmapheresis) that includes antibodies against SARS-CoV-2 for direct transfusion and other antibodies (passive immunity) to patients with severe symptoms of the disease. b plasma from a group of donors could be used to identify and purify specific antibodies against SARS-CoV-2, eliminating other antibodies and proteins, making this method an alternative for passive immunization
Fig. 4
Fig. 4
Schematic representation of the homotrimeric S structure. The S protein conformations with all “down” (left) and all “up” (right) RBDs were generated with PDB files 7k90 and 7k4n, respectively. The RBM of RBD (center) is highlighted as an orange surface
Fig. 5
Fig. 5
Classes of antibodies according to the binding pose. Coordinates for antibodies CC12.1 (Class1), CV07-270 (Class 2 tertiary), C002 (Class 2 quaternary), S309 (Class 3), and CR3022 (Class 4) were taken from PDB files 6xc2, 6xkp, 7k8t, 6wpt, and 6yro, respectively
Fig. 6
Fig. 6
A proposed simplified bioprocess flow diagram for an anti-SARS-CoV-2 monoclonal antibody production: 0. Inoculum train and culture media preparation. 1. Production bioreactor. 2. Cell harvesting (centrifugation or filtration). 3. Affinity (Protein-A) purification. 4. Low pH viral inactivation. 5. Ion exchange chromatography. 6. Virus removal. 7. Ultrafiltration / diafiltration and 8. Active Pharmaceutical Ingredient (API) formulation
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