Vaccine is the ultimate tool to control the coronavirus infection or covid-19. As of June 9, 2020, there are 10 candidate coronavirus vaccines in clinical evaluation and 126 candidate vaccines in preclinical evaluation based on World Health Organization.
With full supports from all, it is optimistic that a viable coronavirus vaccine may be ready for general public soon.
With plentiful funding, all possible approaches to develop a safe and effective coronavirus vaccines are under study. Collaborations among academy, government, and industry lead to swift development of the coronavirus vaccines.
So far, all vaccine candidates are targeting the spike (S) protein of the SARS-Cov-2. Here are the vaccine technologies employed to express the protein and to develop the coronavirus vaccines:
- Coronavirus based vaccines: Inactivated virus and attenuated or weakened virus
- Vector based vaccines: Replicating and non replicating
- Nucleic acid based vaccines: DNA and RNA
- Protein based vaccines: Protein subunit, virus-like particle (VLP), and peptide
Coronavirus based vaccines
– Inactivated virus
In this class of vaccines, the virus is inactivated using chemicals, such as formaldehyde. To make the vaccines, large quantities of infectious virus are required. The is one of the most well-established methods for vaccine development.
The following companies are making inactivated coronaivrus vaccines:
- Beijing Institute of Biological Products, Beijing
- Institute of Medical Biology, Chinese Academy of Medical Sciences, Beijing
- Sinovac Biotech, Beijing
- Wuhan Institute of Biological Products, Wuhan
– Attenuated or weakened virus
A number of techniques allow to weaken the coronavirus, making it less able to cause disease, but maintaining its replication capacities and immunogencity.
Codagenix, Farmingdale, New York, collaborates with the Serum Institue of India, Pune, to weaken the covid-19 by altering its genetic code, which reduces the virus infectivity.
Vector based vaccines
Vectors are used to express the S protein. There are two types: those that can replicate and those that cannot replicate within cells due to key gene inactivation.
– Replicating vector
Merck, Kenilworth, NJ, uses vesicular stomatitis virus (VSV) vector to deliver the S protein. The product is in preclinical investigation.
Intravacc, Bilthoven, The Netherlands, employs the Newcastle disease virus (NDV) vector to express the S protein. The product is in preclinical investigation.
Janssen, Raritan, NJ, develops its coronavirus vaccine, Ad26.COV2-S, using a modified adenovirus vector. The product is in phase 1 clinical trial.
– Non-replicating vector
Partnereing with Univesity of Oxford, AstraZeneca, develops coronavirus vaccine, ChAdOx1 nCoV-19 or AZD1222, using adenovirus vector. The vaccine is under phase III clinical trial.
CanSino Biologics, Tianjin, works on the coronavirus vaccine using adenovirus type 5 vector. The vaccine is under phase II clinical trial.
Nucleic acid based vaccines
The nucleic acid containing genetic codes for the S protein is inserted into human cells and is expressed the S protein, which is acted as vaccine to generate immune response against the virus.
Plasmid containing the S protein gene introduced into human cells. The gene is transcribed into mRNA, which is translated into S protein.
Inovio, Plymouth Meeting, PA, is developing a DNA vaccine, INO-4800. Their technology uses DNA contenting the genetic code of S protein.
The vaccine is delivered into human cells by a device using a brief electrical pulse to open small pores in the skin. Once the DNA is inside cell, it is transcripted into mRNA, then is translated into S protein, which stimulates the body’s generating immune response to the protein.
INO-4800 is in phase I clinica trial.
RNA containing the S protein gene is encased in a lipid coat, introducing into the human cells. The RNA is translated into protein.
Modera, Cambridge, MA, is a leader in the field of RNA vaccine. Working with the National Institute of Alleggy and Infectious Diseases, Modera is developing mRNA-1273, carrying messenger RNA or instruction codes to make the S protein.
MRNA-1273 is in phase II clinical trial.
Pfizer and BioNTech works together to test four vaccines, with different S protein genes, or mRNA.
The vaccine, BNT162 is in phase II clinical trial.
Protein based vaccines
– Protein subunit
The focus is on the S protein or key portion of the protein called the receptor binding domain.
Sanofi Pasteur, Paris, France, and GSK, Brentford, UK, uses baculovirus expression system to express the S protein, which is purified as vaccine.
Empty virus shells mimic the coronavirus structure, but aren’t infectious because they lack genetic material.
Novavax, Gaitheresburg, MD, develops a coronavirus vaccine, NVX-CoV2373, using VLP technology. The VLP contains projections of the S protein. NVX-CoV2373 is in phase II clinical trial.
Flow Pharma, Pleasant Hill, CA, is developing FlowVax COVID-19, a vaccine designed to generate a immune response against SARS-CoV-2 infection.
Generex, Burlington, Canada, employs their li-Key technology generating synthetic peptide vaccine.
- Draft landscape of COVID-19 candidate vaccines: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines
- The race for coronavirus vaccines – a graphical guide: https://www.nature.com/articles/d41586-020-01221-y