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 https://doi.org/10.47488/dhrp.v1iS5.37 

  
 

http://dhrproceedings.org 11 © DHR Health Institute for Research and Development 
 

 

COMMENTARY 

What is the Definition of being Fully 
Vaccinated?  

Should the Three-dose Vaccination 
with the mRNA Vaccines be the New 
Standard? 
Sohail Rao, MD, MA, DPhil1, 2 and Manish Singh, MD, FACS3 

 1 Executive Vice President, DHR Health, 5501 S. McColl Road, Edinburg, Texas 78539 and President 
& Chief Executive Officer, DHR Health Institute for Research & Development, 5323 S. McColl Road, 
Edinburg, Texas 78539.  
ORCID: https://orcid.org/0000-0001-5027-9992  
2 Correspondence should be addressed to: Sohail Rao, MD, MA, DPhil., DHR Health Institute for 
Research & Development, 5323 S. McColl Road, Edinburg, Texas 78539. Tel: (956) 362-2387. E-mail: 
s.rao@dhr-rgv.com  
3 Chief Executive Officer, DHR Health, 5501 S. McColl Road, Edinburg Tx 78539 and DHR Health 
Bariatric & Metabolic Institute, 5500 Raphael Drive, Edinburg, TX 79539 
ORCID: Manish Singh: https://orcid.org/0000-0003-4146-3282  
 
Received 12/10/2021 
Accepted for publication 12/10/2021 
Published 12/10/2021 

Keywords:  COVID-19; SARS-CoV-2; B.1.1.529; Omicron variant; CDC: Canters for Disease Control and Prevention; FDA: U.S. Food 
and Drug Administration; Pfizer/BioNTech; Moderna; Jansen

Despite the availability of numerous clinically effective 
COVID-19 vaccines which have been approved and/or 
authorized for use in humans, mitigating morbidity and 
mortality associated with the exposure to or infection with 
SARS-CoV-2 virus remains an elusive global challenge.  It is 
quite alarming that worldwide, over 5.2 million people have 
already died as a result of SARS-CoV-2 infection and over 
8,000 continue to meet this tragic fate every day (1).   In the 
US, over 790,000 have died as a result of COVID-19 and over 
1,000 people are dying every day as a consequence of 
infection with SARS-CoV-2 (2). 

In the US, three COVID-19 vaccines have been approved 
and/or authorized by the FDA and the CDC (Table 1). Using 
the currently recommended criteria, as of December 10, 2021, 
60.5% (>200,000) of the U.S. population has been fully 
vaccinated (Table 1) and 71.5% have received at least one 
dose of the COVID-19 vaccine (2). It is perturbing that 

multiple clinical studies have demonstrated the decline in 
vaccine protection against SARS-CoV-2 infection (3, 4). A 
large cohort study by Chemaitelly, et.al., using subjects who 
received Pfizer vaccine showed that in the first two weeks 
after the first dose of the vaccine, vaccine effectiveness against 
the wild-type and any SARS-CoV-2 variant was undetectable 
(3). However, seven days later, it increased to 36.8%, peaking 
at 77.5% in the four weeks after the second dose. Interestingly, 
regardless of the age group, vaccine effectiveness against the 
wild-type SARS-CoV-2 and all its variants (including Delta) 
gradually decreased after one month, with the decline 
accelerating after month four, to only about 20% after five to 
six months following the second dose (3). 

In Israel, Levin, et.al., studied 4,868 vaccinated healthcare 
workers over the period of approximately six months (4). The 
subjects were tested monthly for anti-spike immunoglobulin 
G (IgG) and neutralizing antibodies against SARS-CoV-2. A  

https://orcid.org/0000-0001-5027-9992
mailto:s.rao@dhr-rgv.com
https://orcid.org/0000-0003-4146-3282


DHRP, 2021, Vol. 1 (S5) 11-14  Definition of Fully Vaccinated? 

 
  

 
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Table 1: FDA and CDC Approved and/or Authorized COVID-19 Vaccines in the United States 

 
Pfizer BioNTech 

(ComirnatyTM) 
Moderna 

Jansen  

(Johnson and Johnson) 

Type of Vaccine mRNA mRNA Viral Vector 

Primary Series of 

Immunization 

Two (2) Doses 

21 days apart 

Two (2) Doses 

28 days apart 
One (1) Dose 

Approved (age) >16 years NO NO 

Authorized (age) >5 years >18 years >18 years 

Booster or 3rd Dose >16 years* >18 years* >18 years** 

Current Definition of 

Fully Vaccinated 

Two (2) weeks 

 after 2nd dose 

Two (2) weeks  

after 2nd dose 

Two (2) weeks  

after 1st dose 

*At least six (6) months after completing the primary series of immunization 
**At least two (2) months after receiving the first dose of the vaccine

very small cohort of healthcare workers (0.4%) were 
diagnosed as having a COVID-19 breakthrough infection. The 
mean IgG level during days four through 30 after two Pfizer 
vaccine doses was 29.3 as a sample-to-cutoff ratio. IgG 
concentrations fell substantially each month and had 
decreased by a factor of 18.3 after six months. 

Similarly, neutralizing antibody titers dropped by a factor of 
3.9 between the peak and the end of the study but declined 
more slowly from months 3 to 6. Expressed as a 50% 
neutralizing level, the mean concentration of neutralizing 
antibodies was 557.1 at the peak, decreasing to 119.4 by six 
months. Six months after the second dose, neutralizing 
antibody concentrations were much lower in men than in 
women (ratio of means [ROM], 0.64), those 65 years and older 
versus those 18 to 44 years (ROM, 0.58), and 
immunosuppressed vaccinees (ROM, 0.30). From the peak to 
the end of the study, substantially lower IgG levels were tied 
to older age, male sex, and the presence of at least two 
underlying chronic conditions (high blood pressure, diabetes, 
abnormal cholesterol levels, and heart, lung, kidney, or liver 
disease), autoimmune disease, and immunosuppression (4). 

Given these clinical observations, the need for a booster dose 
of the COVID-19 vaccine was being seriously contemplated 

by the scientists and the public policy experts. Israel was 
among the first country to initiate the booster dose of Pfizer 
vaccine for its citizens who were >60 years of age. Bar-On, 
et.al., evaluated over 1.1 million subjects over the age of 60 
who had received the booster dose at least five months after 
completing the primary immunization with the Pfizer vaccine 
(5). Those who received the booster were approximately 19.5-
fold less likely to develop severe COVID-19 as compared to a 
similar age-matched controls who had only received the two 
dose primary series of immunization. Interestingly, booster 
vaccination not only resulted in significant reduction in severe 
COVID-19, but also reduced (11.3-fold) SARS-CoV-2 
infections (5). Similar results supporting the effectiveness of 
the third dose of the Pfizer vaccine in enhancing the protection 
against SARS-CoV-2 infections were also reported by Barda 
et al. (6).  

Based on these and similar clinical observations which 
provided unequivocal evidence underscoring the effectiveness 
of a booster dose of COVID-19 vaccines in enhancing 
protection against SARS-CoV-2 infection, on August 12, 
2021, FDA authorized a 3rd dose of Pfizer and/or Moderna 
vaccine for certain immunocompromised individuals (7). This 
authorization was limited to solid organ transplant recipients 
or those who are diagnosed with conditions that are considered 



DHRP, 2021, Vol. 1 (S5) 11-14  Definition of Fully Vaccinated? 

 
  

 
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to have an equivalent level of immunocompromise. On 
November 19, 2021, CDC modified the authorization 
allowing booster dose for all adults ages 18 years and older 
who received a Pfizer-BioNTech or Moderna vaccine at least 
six months after their second dose (8). Emergency 
authorization for Pfizer-BioNTech COVID-19 Vaccine was 
further modified by the FDA on December 09, 2021, for the 
Pfizer-BioNTech COVID-19 vaccine allowing the use of a 
single booster dose for administration to individuals 16 and 17 
years of age at least six months after completion of primary 
vaccination with the Pfizer-BioNTech COVID-19 vaccine (9).  

The recent identification of Omicron (5.1.1.529) variant of 
SARS-CoV-2 from southern African nations and its rapid 
spread across the globe has alarmed the scientific community 
and the public health experts (10-12). This has also called to 
question the efficacy of the existing COVID-19 vaccines in 
affording protection against this variant. A team of scientists 
from the Africa Health Research Institute tested 14 plasma 
samples from 12 participants, with 6 having no previous 
history of SARS-CoV-2 infection and all were previously 
vaccinated with two doses of Pfizer/BioNTech vaccine (13). 
The results showed a 41-fold decline in antibodies generated 
by the Pfizer vaccine to neutralize the Omicron variant as 
compared to the Delta variant of SARS-CoV-2. Interestingly, 
antibodies in the blood from the six volunteers who had 
previous SARS-CoV-2 infection and were subsequently 
vaccinated were better able to neutralize the virus (13). 

The possibility of immune evasion by the Omicron variant has 
also been predicted by artificial intelligence models that have 
been extensively validated (14). Based on 132 three-
dimensional structures of antibody-receptor binding 
complexes, it was suggested that Omicron may be twice more 
likely to escape current vaccines as compared to the Delta 
variant. In an independent study, Pfizer has claimed that three 
doses of Pfizer-BioNTech COVID-19 vaccine (Group B, 
Figure 1) effectively neutralized the Omicron variant while 
two doses (Group A, Figure 1) showed significantly reduced 
neutralization titers (15). Additionally, the data also indicated 
that the third dose of the Pfizer/BioNTech COVID-19 vaccine 
increased the neutralizing antibody titers by 25-fold as 
compared to two doses against the Omicron variant. 

From the foregoing scientific evidence, we conclude that to 
afford effective protection against various variants of the 
SARS-CoV-2, at a minimum three doses of Pfizer or Moderna 
and two doses of Jansen vaccine would be required. In fact, 
we had previously argued that the Pfizer/BioNTech or 
Moderna COVID-19 vaccines should have been authorized by 
the FDA as a three dose primary vaccination series. Likewise, 
we had also previously suggested that Jansen COVID-19 
vaccine should have been a two dose primary vaccination 
series. Considering the available data, we are also 

recommending that booster dose should be authorized for 
children 5-15 years of age ensuring that they are also 
protected against the SARS-CoV-2 variants. Lastly, we are 
also recommending that the definition of FULLY 
VACCINATED be revised to include three doses of 
Pfizer/BioNTech or Moderna and two doses of Jansen 
COVID-19 vaccines. It is not entirely inconceivable that in 
the very near future, we may require additional doses of 
COVID-19 vaccine that has been tailored to neutralize 
evolving SARS-CoV-2 variants.   

Figure 1: Experimental design to determine the capacity of 
antibodies to neutralize Omicron (B.1.1.529) variant of 
SARS-CoV-2 in subjects vaccinated with two doses (Group 
A) or three doses (Group B) of Pfizer/BioNTech Vaccine 

 

Diclosures 

SR declares no conflicts of interest.  

MS declares no conflicts of interest. 

 

References 

1. WHO Coronavirus (COVID-19) Dashboard. 
https://covid19.who.int/  (Accessed on December 09, 
2021; 15:40 hrs) 

2. COVID Data Tracker. Centers for Disease Control and 
Prevention. CDC Data Tracker. (Accessed on December 
09, 2021; 15:50 hrs) 

https://covid19.who.int/
https://covid.cdc.gov/covid-data-tracker/#datatracker-home


DHRP, 2021, Vol. 1 (S5) 11-14  Definition of Fully Vaccinated? 

  
 

http://dhrproceedings.org 14 © DHR Health Institute for Research and Development 
    
 

3. Chemaitelly H, Tang P, Hasan MR, et. al. Waning of 
BNT162b2 Vaccine Protection against SARS-CoV-2 
Infection in Qatar. N. Engl J Med 2021; 385:e83. DOI: 
10.1056/NEJMoa2114114  

4. Levin EG, Lustig Y, Cohen C, et. al. Waning Immune 
Humoral Responses to BNT162b2 Covid-19 Vaccine 
Over 6 Months. N. Eng J Med 2021; 385:e84 DOI: 
10.1056/NEJMoa2114583 

5. Bar-On YM, Goldberg Y, Mandel M, et.al. Protection of 
BNT162b2 Vaccine Booster Against Covid-19 in Israel. 
N Engl J Med 2021; 385:1393-1400 DOI: 
10.1056/NEJMoa2114255 

6. Barda N, Dagan N, Cohen C, et.al. Effectiveness of a 
Third Dose of the BNT162b2 mRNA COVID-19 Vaccine 
for Preventing Severe Outcomes in Israel: An 
Observational Study. Lancet 2021; 398: 2093-100. DOI: 
10.1016/S0140-6736(21)02249-2 

7. Coronavirus (COVID-19) Update: FDA Authorizes 
Additional Vaccine Dose for Certain 
Immunocompromised Individuals. Aug 12, 2021. FDA 
News Release.  

8. CDC Expands Eligibility for COVID-19 Booster Shots to 
All Adults. Nov 19, 2021. CDC News Release.   

9. Coronavirus (COVID-19) Update: FDA Expands 
Eligibility for Pfizer-BioNTech COVID-19 Booster Dose 
to 16 and 17 Year Olds. Dec 09, 2021. FDA News 
Release.  

10. Cheng, M. What is this New COVID Variant in South 
Africa. November 26, 2021. Associated Press. 
https://www.aol.com/explainer-covid-variant-south-
africa-111307372-142856393.html  

11. Classification of Omicron (B.1.1.529): SARS-CoV-2 
Variant of Concern. World Health Organization. 
November 26, 2021. WHO Statement 

12. Statement from President Joe Biden on the Omicron 
COVID-19 Variant. The White House. November 26, 
2021. Whitehouse Statement 

13. Cele S, Jackson L, Khan K, et.al. SARS-CoV-2 Omicron 
has Extensive but Incomplete Escape of Pfizer BNT 
162b2 Elicited Neutralization and Requires ACE2 for 
Infection. medRxiv 2021.12.08.21267417; DOI: 
10.1101/2021.12.08.2126741715 

14. Chen J, Wang R, Gilby NB, Wei GW. Omicron 
(B.1.1.529): Infectivity, vaccine breakthrough, and 
antibody resistance. ArXiv [Preprint]. 2021 Dec 
1:arXiv:2112.01318v1. PMID: 34873578; PMCID: 
PMC8647651. 

15. Pfizer and BioNTech Provide Update on Omicron 
Variant. Dec 08, 2021. Pfizer/BioNTech News Release 

 

 

 

 

 

https://www.nejm.org/doi/10.1056/NEJMoa2114114
https://www.nejm.org/doi/full/10.1056/NEJMoa2114583
https://www.nejm.org/doi/10.1056/NEJMoa2114255
https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(21)02249-2.pdf
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-vaccine-dose-certain-immunocompromised
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-vaccine-dose-certain-immunocompromised
https://www.cdc.gov/media/releases/2021/s1119-booster-shots.html
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-expands-eligibility-pfizer-biontech-covid-19-booster-dose-16-and-17
https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-expands-eligibility-pfizer-biontech-covid-19-booster-dose-16-and-17
https://www.aol.com/explainer-covid-variant-south-africa-111307372-142856393.html
https://www.aol.com/explainer-covid-variant-south-africa-111307372-142856393.html
https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern
https://www.whitehouse.gov/briefing-room/statements-releases/2021/11/26/statement-by-president-joe-biden-on-the-omicron-covid-19-variant/
https://www.medrxiv.org/content/10.1101/2021.12.08.21267417v1
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8647651/
https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-provide-update-omicron-variant

