Inactivated vaccines are also known as whole killed virus vaccines. They are prepared by protein denaturation, which is performed by chemicals such as formalin, formaldehyde, or β-propiolactone, or by heat and radiation. This destroys the pathogen's ability to infect and replicate, but still retains its ability to act as an immunogen because the inactivation process keeps the pathogen intact. The inactivated pathogen triggers the production of antibodies against the pathogen when the vaccine is injected into humans.1
Inactivated vaccines are among the first vaccines invented to act against viruses. The best known traditional inactivated vaccines include the rabies vaccine which was first introduced in 1885,2 the polio vaccine which was first widely used in 1955,3 and the hepatitis A vaccine which was first approved in 1991.4 The flu vaccines provided by the NHS to adults aged above 18 are also inactivated vaccines.5 The fact that the technique in developing inactivated vaccines has long been established makes them one of the attractive types of vaccines prepared in the market today.
There are now 5 inactivated-vaccine candidates for COVID-19 in clinical trials (as of 20th August),6 four developed by biotech companies from China and one from India. Let us have a look at the progress of the testing of these vaccine candidates.
Inactivated vaccines in clinical trials
1. CoronaVac by Sinovac Biotech Co. Ltd.*
CoronaVac was developed by inactivating SARS-CoV-2 using formalin. The vaccine uses aluminium sulfate as an adjuvant to help boost the immune response (alum-adjuvanted); results from clinical trials indicated that two injections, 14 days apart, are needed for best results.
Currently the vaccine candidate is in its phase 3 trials to test the efficacy and safety in Brazil (trials started from 20th July) and Indonesia (trials started from early August). The company is partnered with the Butantan Institute, a public research institute recognized in Brazil for work in vaccines, to recruit 9000 healthcare professionals working in COVID-19 specialized facilities.7 In around July, Brazil became the second country with the most COVID-19 confirmed cases, thus providing sufficient volunteers to speed up the vaccine's development. Analysts remarked that under the current emergency circumstances, phase 3 trials in Brazil could last less than a semester. CoronaVac might be ready for regulatory approval early next year if all goes well.7 Sinovac also partnered with PT Bio Farma, a state-run pharmaceutical company in Indonesia, to recruit up to 1620 volunteers, age between 15 and 59, to run clinical tests of CoronaVac. Indonesia is a country with the world's fourth biggest population and has a high number of COVID-19 infections. The entire process is expected to complete around the coming new year.8
Previous phase 2 clinical trials for CoronaVac demonstrated that the vaccine is well tolerated, with relatively lower incidence rate of fever compared with other COVID-19 vaccine contenders, and without any notable dose-related safety concerns from 743 healthy volunteers aged 18 to 59. The result was published and is currently available as a medRxiv preprint.9
Sinovac is a Beijing-based pharmaceutical company established in 2001 by its Chief Executive Officer Mr. Weidong Yin and the team at Tangshan Yian Biological Engineering Co. Ltd. According to the Sinovac's website, the company has developed and commercialized 6 human-used vaccines over the past two decades. All are inactivated vaccines. Healive, a vaccine against hepatitis A, is their first vaccine product which was first launched in 2002 and took 20 years to research and develop. With the advancing of their technique, they only used about 6 months to complete clinical trials and obtained a production license from China SFDA for PANFLU.1®, a vaccine against H1N1, when a H1N1 influenza broke out in Mexico in March 2009. This is a good example to show their core R&D competence. Their latest vaccine product, Inlive, is a vaccine against enterovirus 71, which causes severe hand, foot, and mouth disease among children.
The company has developed a SARS vaccine which went into phase 1 trials. Although the project was discontinued due to the sudden disappearance of the disease, the experience from 17 years ago benefits Sinovac in developing the COVID-19 vaccine, given that SARS-CoV-2 is very similar to the SARS virus. Moreover, the company obtained one billion renmibi (approximately USD140 million) from the Chinese government and contributions from international NGOs.10
However, if CoronaVac is approved to be used, the accessibility of the vaccine is likely to be a big issue. Almost a decade would be needed to vaccinate every person in China, as at least two doses will be required to immunize each person whereas the company can produce only 300 million doses per year.10
Moreover, it is noteworthy that the company may not be able to run stably. There has been a dispute between the company and its investors since 2018, and its stock in Nasdaq has been frozen since February 2019 and has not since reopened.11
*Information obtained mostly from Sinovac's own website unless otherwise stated. Sinovac's webpage is www.sinovac.com
References
1. Vaccination strategies to combat novel corona virus SARS-CoV-2. Life Sciences 256 (2020), 117956
2. G.L. Geison. Pasteur's work on rabies: Reexamining the ethical issues. The Hastings Center Report. Vol.8, No.2, (April, 1978), p.26-33.
3. Monto AS. Francis field trial of inactivated poliomyelitis vaccine: background and lessons for today. Epidemiol Rev.,1999;21:7-23.
4. P. Vandana, D. Prajakta, and J. Ratnesh. Nanoparticulate drug delivery perspectives on the transition from laboratory to market. Oxford: Woodhead Pub. p212. ISBN 9781908818195.
5. Flu vaccine overview. NHS. https://www.nhs.uk/conditions/vaccinations/flu-influenza-vaccine/
6. Draft landscape of COVID-19 candidate vaccines. World Health Orgainzation. 20 August 2020. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines
7. China's Sinovac phase III trials in Brazil could take as little as three months. Sergio Held and Elise Mak. BioWorld, 10 June, 2020. https://www.bioworld.com/articles/436374-chinas-sinovac-phase-iii-trials-in-brazil-could-last-as-little-as-three-months
8. Indonesia joins Sinovac to initiate phase 3 testing of CoronaVac while securing option to purchase 100m doses. Trial Site News, 23 July, 2020. https://www.trialsitenews.com/indonesia-joins-sinovac-to-initiate-phase-3-testing-of-coronavac-while-securing-option-to-purchase-100m-doses/
9. Y.J. Zhang, G. Zeng, H.X. Pan, et al. mmunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 years: Report of the randomized, double-blind, and placebo-controlled phase 2 clinical trial. MedRxiv. doi: https://doi.org/10.1101/2020.07.31.20161216
10. "We will share our vaccine with the world." Inside the Chinese biotech firm leading the fight against COVID-19. Charlie Campbell. Time, 27 July, 2020. https://time.com/5872081/sinovac-covid19-coronavirus-vaccine-coronavac/
11. A vaccine with a poison pill. Matt Levine. Bloomberg, 22 May, 2020. https://www.bloomberg.com/opinion/articles/2020-05-22/a-vaccine-with-a-poison-pill
Inactivated vaccines are among the first vaccines invented to act against viruses. The best known traditional inactivated vaccines include the rabies vaccine which was first introduced in 1885,2 the polio vaccine which was first widely used in 1955,3 and the hepatitis A vaccine which was first approved in 1991.4 The flu vaccines provided by the NHS to adults aged above 18 are also inactivated vaccines.5 The fact that the technique in developing inactivated vaccines has long been established makes them one of the attractive types of vaccines prepared in the market today.
There are now 5 inactivated-vaccine candidates for COVID-19 in clinical trials (as of 20th August),6 four developed by biotech companies from China and one from India. Let us have a look at the progress of the testing of these vaccine candidates.
Inactivated vaccines in clinical trials
1. CoronaVac by Sinovac Biotech Co. Ltd.*
CoronaVac was developed by inactivating SARS-CoV-2 using formalin. The vaccine uses aluminium sulfate as an adjuvant to help boost the immune response (alum-adjuvanted); results from clinical trials indicated that two injections, 14 days apart, are needed for best results.
Currently the vaccine candidate is in its phase 3 trials to test the efficacy and safety in Brazil (trials started from 20th July) and Indonesia (trials started from early August). The company is partnered with the Butantan Institute, a public research institute recognized in Brazil for work in vaccines, to recruit 9000 healthcare professionals working in COVID-19 specialized facilities.7 In around July, Brazil became the second country with the most COVID-19 confirmed cases, thus providing sufficient volunteers to speed up the vaccine's development. Analysts remarked that under the current emergency circumstances, phase 3 trials in Brazil could last less than a semester. CoronaVac might be ready for regulatory approval early next year if all goes well.7 Sinovac also partnered with PT Bio Farma, a state-run pharmaceutical company in Indonesia, to recruit up to 1620 volunteers, age between 15 and 59, to run clinical tests of CoronaVac. Indonesia is a country with the world's fourth biggest population and has a high number of COVID-19 infections. The entire process is expected to complete around the coming new year.8
Previous phase 2 clinical trials for CoronaVac demonstrated that the vaccine is well tolerated, with relatively lower incidence rate of fever compared with other COVID-19 vaccine contenders, and without any notable dose-related safety concerns from 743 healthy volunteers aged 18 to 59. The result was published and is currently available as a medRxiv preprint.9
Sinovac is a Beijing-based pharmaceutical company established in 2001 by its Chief Executive Officer Mr. Weidong Yin and the team at Tangshan Yian Biological Engineering Co. Ltd. According to the Sinovac's website, the company has developed and commercialized 6 human-used vaccines over the past two decades. All are inactivated vaccines. Healive, a vaccine against hepatitis A, is their first vaccine product which was first launched in 2002 and took 20 years to research and develop. With the advancing of their technique, they only used about 6 months to complete clinical trials and obtained a production license from China SFDA for PANFLU.1®, a vaccine against H1N1, when a H1N1 influenza broke out in Mexico in March 2009. This is a good example to show their core R&D competence. Their latest vaccine product, Inlive, is a vaccine against enterovirus 71, which causes severe hand, foot, and mouth disease among children.
The company has developed a SARS vaccine which went into phase 1 trials. Although the project was discontinued due to the sudden disappearance of the disease, the experience from 17 years ago benefits Sinovac in developing the COVID-19 vaccine, given that SARS-CoV-2 is very similar to the SARS virus. Moreover, the company obtained one billion renmibi (approximately USD140 million) from the Chinese government and contributions from international NGOs.10
However, if CoronaVac is approved to be used, the accessibility of the vaccine is likely to be a big issue. Almost a decade would be needed to vaccinate every person in China, as at least two doses will be required to immunize each person whereas the company can produce only 300 million doses per year.10
Moreover, it is noteworthy that the company may not be able to run stably. There has been a dispute between the company and its investors since 2018, and its stock in Nasdaq has been frozen since February 2019 and has not since reopened.11
*Information obtained mostly from Sinovac's own website unless otherwise stated. Sinovac's webpage is www.sinovac.com
References
1. Vaccination strategies to combat novel corona virus SARS-CoV-2. Life Sciences 256 (2020), 117956
2. G.L. Geison. Pasteur's work on rabies: Reexamining the ethical issues. The Hastings Center Report. Vol.8, No.2, (April, 1978), p.26-33.
3. Monto AS. Francis field trial of inactivated poliomyelitis vaccine: background and lessons for today. Epidemiol Rev.,1999;21:7-23.
4. P. Vandana, D. Prajakta, and J. Ratnesh. Nanoparticulate drug delivery perspectives on the transition from laboratory to market. Oxford: Woodhead Pub. p212. ISBN 9781908818195.
5. Flu vaccine overview. NHS. https://www.nhs.uk/conditions/vaccinations/flu-influenza-vaccine/
6. Draft landscape of COVID-19 candidate vaccines. World Health Orgainzation. 20 August 2020. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines
7. China's Sinovac phase III trials in Brazil could take as little as three months. Sergio Held and Elise Mak. BioWorld, 10 June, 2020. https://www.bioworld.com/articles/436374-chinas-sinovac-phase-iii-trials-in-brazil-could-last-as-little-as-three-months
8. Indonesia joins Sinovac to initiate phase 3 testing of CoronaVac while securing option to purchase 100m doses. Trial Site News, 23 July, 2020. https://www.trialsitenews.com/indonesia-joins-sinovac-to-initiate-phase-3-testing-of-coronavac-while-securing-option-to-purchase-100m-doses/
9. Y.J. Zhang, G. Zeng, H.X. Pan, et al. mmunogenicity and Safety of a SARS-CoV-2 Inactivated Vaccine in Healthy Adults Aged 18-59 years: Report of the randomized, double-blind, and placebo-controlled phase 2 clinical trial. MedRxiv. doi: https://doi.org/10.1101/2020.07.31.20161216
10. "We will share our vaccine with the world." Inside the Chinese biotech firm leading the fight against COVID-19. Charlie Campbell. Time, 27 July, 2020. https://time.com/5872081/sinovac-covid19-coronavirus-vaccine-coronavac/
11. A vaccine with a poison pill. Matt Levine. Bloomberg, 22 May, 2020. https://www.bloomberg.com/opinion/articles/2020-05-22/a-vaccine-with-a-poison-pill
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