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 https://doi.org/10.47488/dhrp.v1iS5.31 

  
 

http://dhrproceedings.org 1 © DHR Health Institute for Research and Development 
 

 

EDITORIAL 

Is There Any Advantage of Using Polyclonal vs. Monoclonal Antibodies for 
Passive Enhancement of Immunity in Patients with COVID-19? 

 
On November 08, 2020, the US Food & Drug 
Administration (FDA) approved the use of first 
monoclonal antibody – Bamlanivimab (LY-
CoV555; Eli Lilly & Company) for the treatment of 
high-risk patients with mild-moderate SARS-CoV-
2 infection (1). Subsequently, on November 23, 
2020, FDA approved another cocktail of 
monoclonal antibodies – Casirivimab + Imdevimab 
(REGEN-COV; Regeneron Pharmaceuticals) for 
use in a similar cohort of high-risk patients with 
mild-moderate COVID-19. Since the initial 
Emergency Use Authorizations (EUA), FDA has 
made numerous modifications/amendments 
including revoking the authorization for 
monotherapy with Bamlanivimab (3); addition of 
Etesevimab to Bamlanivimab monotherapy; and 
authorization of another monoclonal antibody – 
Sotrovimab (Xevudy; Glaxo, Smith & Kline) (4), 
The primary objective of these emergency 
authorizations was to treat patients early in the 
course of the disease in an non-hospitalized setting 
thus mitigating the progression of COVID-19 to a 
more severe stage that would necessitate 
hospitalization.  

With the availability of these monoclonal 
antibodies, we at DHR Health proceeded to obtain 
approval of a prospective study from the DHR 
Health Institute for Research & Development 
Institutional Review Board to treat high-risk 
patients with mild-moderate COVID-19. The first 
patient was treated on November 25, 2020, and 
since then, we have infused anti-SARS-CoV-2 
monoclonal antibodies in over 580 patients with 
very satisfactory outcomes. This included both 
patients who had mild-moderate SARS-CoV-2 
infection as well for post-exposure prophylaxis in 
COVID-19 negative subjects. 

While effective, monoclonal antibodies have 
inherent advantages and disadvantages when used 
for therapeutic purposes. Produced in vitro from 

immortalized plasma cells, monoclonal antibodies 
have single specificity and affinity which, reduces 
the probability of cross reactivity (Figure 1). Due to 
batch-to-batch homogeneity, effectiveness of 
monoclonal antibodies is much more predictable, 
and they serve as an ideal candidate for use in 
diagnostic immunoassays. A distinct disadvantage 
of monoclonal antibodies is the fact that due to 
its high specificity and affinity, a minor mutation 
in the epitope often renders the antibody 
ineffective in neutralizing the target. This is a 
serious limitation since observed mutations in 
SARS-CoV-2 with generations of numerous 
variants may render the available monoclonal 
antibodies less effective in mitigating the 
progression of COVID-19. On the contrary, 
polyclonal antibodies are a mixture of monoclonal 
antibodies that are products of multiple B cell 
clones. Generated in animals, polyclonal antibodies 
recognize with reasonably high affinity multiple 
epitopes on a single antigen (Figure 1). This 
affords polyclonal antibodies a distinct 
advantage over monoclonal antibodies when 
used as therapeutic agents particularly in 
patients infected with rapidly mutating SARS-
CoV-2 virus.  

 
 

Figure 1: Monoclonal antibody have affinity for a single 
epitope on the antigen (i.e., the virus or the bacteria). On 
the contrary, polyclonal antibodies are a mixture of 
monoclonal antibodies with affinity for various epitopes 
on the antigen. 



DHRP, 2021, Vol. 1 (S5) 1-3  Editorial 

  
 

http://dhrproceedings.org 2 © DHR Health Institute for Research and Development 
    
 

On April 17, 2020, the National Institutes of Health 
(NIH) announced the Accelerating COVID-19 
Therapeutic Interventions and Vaccines (ACTIV) 
public-private partnership to develop a coordinated 
research strategy for prioritizing and speeding 
development of the most promising treatments and 
vaccines. ACTIV was based on Bayesian adaptive 
clinical trial design which allows for frequent 
“looks” at the data and permits data-driven 
modifications during the course of the study (5). 
DHR Health Institute for Research and 
Development is part of the ACTIV collaborative 
and have initiated numerous studies in an attempt to 
find the most promising therapeutic agent to prevent 
and/or treat patients with COVID-19.  

As part of ACTIV-2, DHR Health Institute for 
Research & Development has initiated a 
prospective Phase 2/3 clinical trial to evaluate the 
efficacy of fully human anti-SARS-CoV-2 
polyclonal antibody (SAB-185; SAB 
Pharmaceuticals, Inc.) to treat unvaccinated non-
hospitalized high-risk patients with mild-moderate 
COVID-19. SAB-185 is a fully human, anti-SARS-
CoV-2 immunoglobulin produced in 
transchromosomic bovines (Tc-hIgG-SARS-CoV-
2) hyperimmunized with two doses of plasmid 
DNA encoding the SARS-CoV-2 Wuhan strain S 
gene, followed by repeated immunization with S 
protein purified from insect cells (6,7). The 
resulting Tc-hIgG-SARS-CoV-2, termed SAB-185, 
efficiently neutralizes SARS-CoV-2, and vesicular 
stomatitis virus (VSV) SARS-CoV-2 chimeras in 
vitro. This fully human polyclonal antibody that 
potently inhibits SARS-CoV-2 infection may 
provide an effective therapeutic agent to combat 
COVID-19. This is not a placebo-controlled 
study as the patients in the comparator arm will 
be treated with REGEN-COV monoclonal 
antibody. 

In conclusion, the use of available anti-SARS-CoV-
2 monoclonal antibodies has been effective in 
mitigating the progression of disease in high-risk 
patients with mild-moderate COVID-19. However, 
it could be argued that the use of fully human 
polyclonal antibodies with affinity for multiple 
epitopes on SARS-CoV-2 may be more effective in 
eliminating the virus and its variants which exhibit 

higher transmissibility, infectivity, and the potential 
to “escape” from the neutralizing effects of existing 
experimental agents. 

References  

1. Emergency Use Authorization (EUA) for bamlanivimab 700mg 
IV Center for Drug Evaluation and Research (CDER) Review. 
2020.  https://www.fda.gov/media/144118/download  
(Accessed October 26, 2021). 

2. Emergency Use Authorization for REGEN-COV for the 
treatment of mild-moderate COVID-19. 2020. 
https://www.fda.gov/media/145610/download . (Accessed 
October 26, 2021). 

3. FDA Revokes Initial Emergency Use Authorization of 
Monotherapy with Bamlanivimab. March 2021. 
https://www.fda.gov/media/143602/download  (Accessed 
October 27, 2021). 

4. FDA Authorizes Additional Monoclonal Antibody for 
Treatment of COVID-19. 2021. https://www.fda.gov/news-
events/press-announcements/coronavirus-covid-19-update-fda-
authorizes-additional-monoclonal-antibody-treatment-covid-19 
. (Accessed October 27, 2021). 

5. Giovagnoli A. (2021). The Bayesian Design of Adaptive 
Clinical Trials. International journal of environmental research 
and public health, 18(2), 530. 
https://doi.org/10.3390/ijerph18020530   

6. Gilliland T, Liu Y, Li R, Dunn M, Cottle E, Terada Y, Rickman 
Z, Alcorn M, Vasilatos S, Lundy J, Larson D, Wu H, Luke T, 
Bausch C, Egland K, Sullivan E, Wang Z, Klimstra WB. 
Protection of human ACE2 transgenic Syrian hamsters from 
SARS CoV-2 variants by human polyclonal IgG from hyper-
immunized transchromosomic bovines. bioRxiv [Preprint]. 
2021 Jul 26:2021.07.26.453840. doi: 
10.1101/2021.07.26.453840. PMID: 34341790; PMCID: 
PMC8328057. 

7. Liu Z, Wu H, Egland KA, Gilliland TC, Dunn MD, Luke TC, 
Sullivan EJ, Klimstra WB, Bausch CL, Whelan SPJ. Human 
immunoglobulin from transchromosomic bovines 
hyperimmunized with SARS-CoV-2 spike antigen efficiently 
neutralizes viral variants. Hum Vaccin Immunother. 2021 Jul 
6:1-10. doi:10.1080/21645515.2021.1940652. Epub ahead of 
print. PMID: 34228597; PMCID: PMC8290372. 

Sohail Rao, MD, MA, DPhil 

Executive Vice President, DHR Health, 5501 S. McColl 
Road, Edinburg, Texas 

President & Chief Executive Officer, DHR Health 
Institute for Research & Development, 5323 S. McColl 
Road, Edinburg, Texas 

Corresponding author email: s.rao@dhr-rgv.com 

Disclosures: None 

ORCID: Sohail Rao: https://orcid.org/0000-0001-5027-
9992 

 

 

https://www.fda.gov/media/144118/download
https://www.fda.gov/media/145610/download
https://www.fda.gov/media/143602/download
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-monoclonal-antibody-treatment-covid-19
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-monoclonal-antibody-treatment-covid-19
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-monoclonal-antibody-treatment-covid-19
https://doi.org/10.3390/ijerph18020530
https://orcid.org/0000-0001-5027-9992
https://orcid.org/0000-0001-5027-9992


DHRP, 2021, Vol. 1 (S5) 1-3  Editorial 

 
http://dhrproceedings.org 3 © DHR Health Institute for Research and Development 

Caitlin White 

DHR Health Institute for Research & Development, 
5323 S. McColl Road, Edinburg, TX 78539. 

Disclosures: None 

ORCID: Caitlin White: https://orcid.org/0000-0001-
5528-2242  

Manish Singh, MD, FACS 

Chief Executive Officer, DHR Health, 5501 S. McColl 
Road, Edinburg, Texas 

DHR Health Bariatric & Metabolic Institute, 5500 
Raphael Drive, Edinburg, TX 79539 

Disclosures: None 

ORCID: Manish Singh: https://orcid.org/0000-0003-
4146-3282 

https://orcid.org/0000-0001-5528-2242
https://orcid.org/0000-0001-5528-2242

