Protein Subunit Vaccines: Why They’re More Important Than Ever

On Monday, December 27, 2021, the United Arab Emirates approved a new vaccine to be produced and distributed by Hayat Biotech, a joint venture between Abu Dhabi-based G42 and Sinopharm CNBG. It uses the recombinant protein subunit platform, similar to widely used influenza and hepatitis B vaccines, and will be available to the public as a booster dose from January 2022.
Image credit: AFP
Strong points
- New crop of protein-based COVID vaccines expands global vaccine choices.
- The advantages of protein subunit vaccines include high efficacy rate, safety, ease of production / distribution and relatively lower cost.
- Protein subunit vaccines dramatically expand humanity’s arsenal to fight the pandemic, especially in poor countries.
Vaccines work by exposing the body to molecules of the target pathogen to trigger an immune response. But the method of exposure varies.
Against SARS-CoV-2, there are so far four types of vaccine platforms: virus-based, vector-based, nucleic acid-based and protein-based.
On Monday, December 27, 2021, the United Arab Emirates approved CNBG Sinopharm’s COVID-19 vaccine using the recombinant protein subunit platform. It would be used as a booster for people previously inoculated with two doses of Sinopharm’s inactive jab, according to the United Arab Emirates Department of Health and Prevention (MoHAP). Here is the truth about this class of vaccines:
How does a protein subunit vaccine work?
In a nutshell, a protein subunit vaccine exploits tiny particles containing several artificial spikes grown in cell cultures and then uses them as a vaccine against an illicit immune response in the recipient’s body. Sinopharm’s new recombinant protein vaccine uses the Spike (S) protein that surrounds the SARS-CoV-2 virus. This helps the body to identify the virus and then fight it off if exposed. The technology makes it possible to avoid several variations.

Image Credit: Elsevier / ScienceDirect / Gulf News
It is generally made by recombinant synthesis of protein “antigens” (molecules that trigger an immune response), as well as by methods of protein isolation and purification, Nature Explain. “Recombinant” means to use genetic engineering to produce the new vaccine. This is usually done by inserting genetic material of protein S into the genetic material of another organism (yeast, bacteria).
This is achieved by culturing large amounts of the pathogen (disease causing agent i.e. virus / bacteria, in this case SARS-CoV-2). The genetically modified organism produces the S protein, which is then extracted, purified and introduced as an active ingredient in the vaccine.
Today, the best-known example of this vaccine development strategy are the subunit influenza vaccines.
JOINT VENTURE
Study: A United Arab Emirates-based study showed an immune response against emerging variants of the virus in volunteers who had previously received two doses of inactivated Sinopharm CNBG vaccine.
Booster dose: The new vaccine will be produced and distributed by Hayat Biotech, a joint venture between G42 and Sinopharm CNBG.
Availability: The vaccine will be available to the public as a booster dose from January 2022.

There is an abundance of candidate SARS-CoV-2 protein subunit vaccines in human clinical trials – as well as those approved. There are 13 ongoing clinical trials and 6 have been approved in at least 1 state / territory.
It is a proven vaccine platform. It is also quite common. Currently, the WHO lists at least about 70 candidate subunit protein vaccines against SARS-CoV-2.
Each exploits a different immunogen – primarily various forms of the entire Spike (S) protein or its receptor binding domain (RBD), the region of the S protein that mediates viral binding to the ACE2 receptor of target host cells.
227.87
number of doses per 100 people: the rate of vaccine distribution in the UAE
Upon binding to the ACE2 receptor of the host cell, the pre-fusion conformation of protein S undergoes an extensive conformational change to a highly stable post-fusion conformation which allows fusion between the viral particle and the membranes of the host cell.
More immunogenic
Write for Nature, Nikolaos C. Kyriakidis of One Health Research Group, Universidad de Las Américas (UDLA), Quito, Ecuador, and colleagues explained, “As a general rule, pre-fusion stabilized viral glycoproteins are generally more immunogenic, making them more attractive vaccine targets. “
100%
Percentage of the eligible population in the United Arab Emirates who received the first dose of COVID vaccine.
What vaccines use the protein subunit development platform?

The best known and most proven examples of the protein subunit vaccine development strategy are the influenza subunit vaccines.
The first forms of protein subunit vaccines developed aimed to harness the ability of protein antigens to trigger immunoglobulins (aka antibodies). In the 1960s, one of the earliest examples of an “acellular vaccine” was the protective anthrax antigen.

Image Credit: Gulf News
The technique, developed in the 1960s, gained ground in the 1990s with the explosion of genetic engineering, allowing the cloning and acceleration of the production of antigens in vitro (in a test tube, box or elsewhere outside of a living organism).
22.5m
COVID-19 vaccine doses administered in the United Arab Emirates as of December 28, 2021
This led to the production of large amounts of the hepatitis B surface antigen in yeast cells – a breakthrough that led to the production of the hepatitis B vaccine.
An “adjuvant” (enhancement of efficacy / potency) is usually added to elicit a robust immune response.
How many protein subunit vaccines have been approved?
So far, the development of a high-speed COVID vaccine has relied on inactivated virus (Sinopharm, Sinovac), nucleic acid (Pfizer, Moderna mRNA) or vectors (AstraZeneca, Sputnik V) strategies. Today, there are at least 10 other PS-based vaccines approved in at least one state / territory:
1. Anhui Zhifei Longcom ZF2001 (approved in [3]: China, Indonesia, Uzbekistan)
2. Novavax NVX-CoV2373 (approved in [30]: Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal , Romania, Slovakia, Slovenia, Spain and Sweden)
3. Instituto Finlay de Vacunas Cuba: Soberana Plus (approved in [1]: Cuba)
4. Instituto Finlay de Vacunas Cuba: Soberana 02 (approved in [4]: Cuba, Iran, Nicaragua, Venezuela)
5. Razi Vaccine and Serum Research Institute: Razi Cov Pars (approved in [1]: Iran)
6. Serum Institute of India: COVOVAX / Novavax formulation (approved in [2]: Indonesia, Philippines)
7. FBRI: EpiVacCorona (approved in [2]): Russian Federation, Turkmenistan)
8. Center for Genetic Engineering and Biotechnology (CIGB): CIGB-66 (approved in [4]: Cuba, Nicaragua, Venezuela, VietNam)
9. Vaxine / CinnaGen Co .: COVAX-19 (approved in [1]: Iran)
10. Medigen: MVC-COV1901 (approved in [1]: Taiwan)
What are the advantages of the protein subunit vaccine?
Protein subunit vaccines offer a number of advantages:
1. Safety:
They are specifically selected for their ability to stimulate immune cells, according to Gavi, the global vaccine alliance. These fragments are incapable of causing disease – as such, subunit vaccines are considered inherently safe.
2. Logistics:
Another big advantage is the logistics: vaccines based on protein subunits do not need supercooling, especially compared to mRNA injections.
91.80%
Percentage of people fully immunized in the United Arab Emirates
3. Simplicity:
Rather than injecting a whole pathogen (disease causing virus / bacteria) to trigger an immune response, PS vaccines – also known as “acellular vaccines” – contain purified pieces of it.
4. Proven production platform / efficiency:
Protein subunit vaccines are already widely used (i.e. hepatitis B vaccine and acellular pertussis). In terms of manufacturing, a PS vaccine is based on a factory-grown protein, which does not require a live (attenuated) or inactivated virus. Attenuated or inactivated vaccines must first grow the virus in huge quantities in stainless steel containers located inside a highly biosecure facility. in vaccine vials.
5. Manufacturing:
PS vaccines are much easier to produce than attenuated or inactivated virus vaccines because facilities with high biosafety levels are not required. However, they must be produced according to the regulations of Current Good Manufacturing Practices (CGMP). This could potentially change the cost equation as well as the distribution.
6. Affordability:
In theory, this could make COVID vaccines more accessible to poor countries. Currently, only 6% of Africa’s 1.216 billion people have been fully vaccinated against COVID-19 so far, the lowest rate among the world’s 7 continents.
A damper : He frequently raises the need to increase booster doses and optimize the added “adjuvant” to achieve stronger and longer lasting immunization.
70
number of protein subunit vaccines under development (Source: WHO)
Latest vaccine development score
168: vaccine candidates
543: vaccine trials
62: countries with vaccine trials
30: approved vaccines
8: cessation of vaccine development projects
Source: covid19.trackvaccines.org
Is the CNBG Recombinant Protein Subunit (RPS) vaccine the first to be approved in China?
No. Laboratory (animal) testing is done before clinical testing (human testing). On April 10, 2021, CNBG obtained regulatory approval for the human testing stage in China for its PS vaccine.
A month earlier, on March 17, 2021, the Recombinant Protein Subunit Vaccine from the Institute of Microbiology of the Chinese Academy of Sciences against COVID-19 was approved by the Beijing government for use in emergency. It was developed by the institute and Anhui Zhifei Longcom Biopharmaceutical, and is the first vaccine using the RPS technique approved by the country for emergency use against COVID-19.
In contrast, Sinopharm’s BBIBP-CorV (Vero cells) has been approved in 80 countries (including the United Arab Emirates); The inactivated vaccine (Vero cells) from Sinopharms (Wuhan) has been approved in 2 countries: China and the Philippines.
Up to 100% seroconversation rate
The Sinopharm CNBG New Recombinant Protein Subunit Vaccine Study included individuals who had previously been vaccinated with two doses of the inactivated Sinopharm CNBG vaccine.
The seroconversion rate was up to 100% neutralizing antibody, as well as high safety rates and no side effects recorded in all participants.