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.
Merck and Themis Bioscience develop a vaccine using the measles virus to carry genetic material into patients’ cells.
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.
Novartis is developing a vaccine based on a gene therapy treatment by the Massachusetts Eye and Ear Hospital. A virus called an adeno-associated virus delivers coronavirus gene fragments into cells.
Vaxart’s vaccine is an oral tablet containing an adenovirus that delivers coronavirus genes.
– 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.
The Gamaleya Research Institute, part of Russia’s Ministry of Health, developed a vaccine, called Gam-Covid-Vac Lyo, using a combination of two adenoviruses, Ad5 and Ad26, and both vectors are engineered with a coronavirus gene. They started Phase I trial in June 2020.
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.
Japanese company AnGes in partnership with Osaka University and Takara Bio. developed a DNA-based vaccine. They started human clinical trials on June 30, 2020.
Indian vaccine-maker Zydus Cadila has created a DNA-based vaccine. They start human trials on July 3, 2020.
The Korean company Genexine developed a DNA vaccine. They started clinical trial in June, 2020.
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.
Morningside Ventures and Imperial College London have developed a “self-amplifying” RNA vaccine. They began Phase I/II trials on June 15, 2020.
CureVac developed a mRNA vaccine. They launched Phase I trials in June 2020.
Chinese researchers at the Academy of Military Medical Sciences, Suzhou Abogen Biosciences and Walvax Biotechnology developed a mRNA vaccine, called ARCoV. They started human clinical trials in June 2020.
Sanofi and Translate Bio is developing an mRNA vaccine.
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.
Chinese company Anhui Zhifei Longcom developed viral protein vaccine.
Clover Biopharmaceuticals, GSK, and Dynavax has developed a vaccine containing a protein from coronaviruses with adjuvants.
Australian company Vaxine developed protein vaccine with an adjuvant. They started Phase I trial in July 2020.
Australia’s University of Queensland, GSK and CSL created viral protein vaccine. They started clinical trial in June 2020.
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.
Medicago, GSK and Dynavax developed plant based VLP vaccine. They started Phase I trials in July 2020.
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.
Self-Experimentation of Covid-19 Vaccine
In the video below, there is discussion on self-experimentation. If you are interested, you could join a Do-It-Yourself vaccine experiment. Here is the LINK for you to learn more.
Covid-19 Vaccine Phase 3 Clinical Trials
Johnson & Johnson is so confident on their covid-19 vaccine that they released their phase 3 covid-19 clinical trial protocol to public. As far as I know, this is the first time for any private companies that released such protocol, which is usually top secret. You can download the protocol here: https://kcancer.com/wp-content/uploads/2020/09/covid-19-phase-3-study-clinical-protocol-JNJ.pdf
Other important features: single dose, while Pfizer, Astrazeneca, and Modera need two doses. 60,000 clinical trial enrollments, which is the highest number among the phase 3 covid-19 vaccine clinical trial.
Please watch the video below to learn more.
Antibody Treatments for Covid-19
Vaccines are effective for preventing covid-19 infection. But after infection, it is too late to apply vaccines since it takes weeks to generate immunity against the virus and in this case, treatments, such as antibodies, should be employed to control the virus infection. The video below discuss antibody treatments for covid-19.
Why Do Clinical Trials Halt?
As of October 13, 2020, there are three high profile covid-19 clinical trials, Johnson and Johnson’s covid-19 vaccine, AstraZeneca’s covid-19 vaccines and Eli Lilly’s antibody treatment, that were halted. The trials were paused due to their severe adverse reactions in the participants. This is a normal clinical trial process. Safety is an ultimate parameter for any drugs to be approved by authority. All clinical trials are designed to protect human subjects from any potential damage. The video below discusses the issues, particularly safety of the vaccines, under clinical trials.
Human Challenge Trial for Covid-19
It is really vital that we move as fast as possible towards getting effective vaccines and other treatments for COVID-19, and human challenge trials have the potential to accelerate the development of novel drugs and vaccines, though there are some bioethical issues with the practices. Would you join a human challenge trial? The video below describes human challenge trial.
- 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