|Year : 2020 | Volume
| Issue : 3 | Page : 200-204
SARS CoV2 vaccine-present scenario
Emeritus Consultant, Department of Pediatrics, Indraprastha Apollo Hospital, New Delhi, India
|Date of Submission||02-Jul-2020|
|Date of Acceptance||08-Jul-2020|
|Date of Web Publication||19-Aug-2020|
Indraprastha Apollo Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
SARS CoV2 virus is responsible for the pandemic of COVID-19 disease and has devastated the entire world. The COVID-19 disease has been responsible for huge number of morbidity and mortality in the world including India. Since there is no specific drug to cure this disease, research and development is going on to find a safe and effective vaccine to prevent the disease. According to the World Health Organization, there are 24 candidate vaccines which are in advance stages of development and 142 are in preclinical stages. There are various platforms in which this novel coronavirus vaccines are underdevelopment, for example, nonreplicating viral vector, RNA, DNA, inactivated, and subunit. In normal situation, it takes minimum 10-year time to develop a new vaccine from conception to first use in the market. In case of SARS CoV2 vaccine, all out efforts are made by all institutions and vaccine manufacturing companies with the help of respective regulatory authorities to reduce the time frame. In all probabilities, few vaccines would be developed in record time and expected to be in the market by the beginning of 2021. In India, there are six candidate vaccines which are in development and all are in various stages. There are several challenges during development and later once it becomes available for human use. This review is an attempt to briefly cover the present stages of development of various vaccines and the challenges that are likely to be encountered.
Keywords: COVID-19, COVID-19 vaccine, SARS CoV2
|How to cite this article:|
Dutta A. SARS CoV2 vaccine-present scenario. Apollo Med 2020;17:200-4
| Introduction|| |
The whole world is now looking for a safe and effective vaccine against COVID-19 disease which is taking a heavy toll of human life. The COVID-19 disease is caused by a novel coronavirus named as SARS CoV2 (severe acute respiratory distress coronavirus 2) which has its origin from Wuhan in China., This is an enveloped positive-sense single-stranded RNA virus that infects humans, bats, and certain other mammals. The most antigenic and infective part is spike (S) protein which is located on the surface of the virus and gives the appearance of crown and hence the name Corona. The spike protein has the capability of binding with angiotensin-converting enzyme 2 protein on human cells and thus causes disease. There is strong evidence that the changes in the S protein allowed the novel coronavirus to jump species and successfully infected humans. Besides S protein, there are also membrane protein (M), nucleocapsid protein (N), envelop protein (E), and a lipid bilayer membrane.
Since the declaration of a pandemic by the World health Organization (WHO), >120 institutions including academic, research, and vaccine manufacturing companies are actively working on different platforms to develop a safe and effective vaccine against SARS CoV2.
| Vaccine Development|| |
The WHO declared on January 30, 2020, that a severe respiratory disorder syndrome originated in Wuhan city as a global public health emergency and on February 11 named the disease as COVID-19. The spread of COVID-19 is now relentless and spread in almost all the countries of the world, causing serious public health, social, and economic problems.
To combat this highly infectious disease, several public health measures have been taken by various countries and simultaneous search is on to find a safe and effective vaccine.
Vaccine is considered to be one of the best armamentaria in public health for prevention of infectious diseases, especially against diseases where effective treatment is not available. Once the pandemic of COVID-19 disease has been confirmed by the WHO, there is a race for development of a safe and effective vaccine against the SARS CoV2 virus. As per the latest, 24 and 142 vaccines are in advance stages in preclinical stages of development. [Table 1] depicts the vaccines which are in advance stages of development. All institutions, research, and academic bodies including vaccine manufacturers involved in vaccine development are working at extra speed to find a safe and effective vaccine which can help in reducing the number of cases and stop the pandemic. It is very easy to state that a vaccine should be produced at the earliest but in practice in a normal circumstance, it takes minimum 5–10 years to go through different hurdles of clinical stages of development of any new vaccine. However, in epidemic and pandemic situation, many of the stages are overlapped and the regulatory authorities respond very quickly at each stage of development. It is therefore expected that in extraordinary situation, it shall still take minimum 12–18 months' time before the vaccine finds its way to the market for human use. Therefore, it is very unlikely that any manufacturer would be able to supply the vaccine before December 2020 or the beginning of 2021. By the time the vaccine is available freely, it may happen that the brunt of the pandemic diminishes, and there may not be a real need for the vaccine as most of the people shall develop herd immunity by either subclinical infection or suffering from the disease of various stages of severity.
|Table 1: Draft landscape of development of COVID 19 candidate vaccines (WHO) in advance stage as of June 21, 2020, 24 and 142 in advance stages and 128 in preclinical stage|
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Most of the development work on a vaccine is taking place in North America (46%), China (18%) and Europe (18%) followed by Asia, including Australia (18%). Coalition for epidemic preparedness initiative (CEPI) is in consultation with several institutions in North America and China for the development of COVID-19 vaccine.,
As per the latest WHO publication, there are 24 COVID-19 vaccines which are in stage 1/2a/3 clinical development and may require anytime between 6 and 12 months to be available for commercial use. There are 142 more COVID-19 candidate vaccines which are underdevelopment in various parts of the world including India. All of these 142 candidate vaccines are in preclinical stage of development. The world shall witness a variety of vaccines against COVID-19 produced in different biotechnological methods, for example, inactivated, vector based, RNA, DNA, subunit, and live depending on the expertise and research experience of individual institutions and laboratories. It may happen that simultaneously all 11 vaccines which are in relatively advance stages of development would be available for use.
The most widely talked vaccine in India is the Oxford University (Jenner laboratory) ChAdOX1 COVID-19 vaccine being developed in nonreplicating vector-based technology, in which a weak chimp adenovirus is identified and the spike protein RNA of SARS CoV2 shall be introduced in it to develop the vaccine. The human stage 2a/3 randomized control trial in humans has already started and the results are expected by the end of September source. The University of Oxford and AstraZeneca, the first to begin phase 3 studies, are focusing primarily on healthy adults aged 18–65, both who work in frontline health-care settings and the general public. Their 10,000 participant trial is already underway in the UK. The trial is also recruiting a small number of older adults and children to start assessing efficacy in these cohorts. In this randomized control trial, one dose of the experimental vaccine is given in the study group and quadrivalent meningococcal conjugate vaccine is administered in the control arm. The initial trial in rhesus macaque which is in print showed that the vaccine prevented monkeys from developing pneumonia and severe form of disease but did not prevent the spread of infection. However, it is too early to translate the same phenomenon in human beings and let us wait for the final result. If the infection cannot be prevented by the vaccine, there may be spread of the disease to a susceptible population and the purpose of pandemic spread may be defeated.
Moderna vaccine in collaboration with the National Institute of Allergy and Infectious Disease in the USA is in advance stage of development of a messenger RNA-based vaccine using two-dose schedule at an interval of 4 weeks and phase 2 clinical trial is already in progress. This vaccine has shown promising results in animals, and safety studies in human subjects did not show any serious adverse reactions.
The CanSino vaccine in collaboration with the Beijing Institute of Biotechnology is in advance stage of development and already in phase 2 trial. The vaccine has been developed under the platform of nonreplicating viral vector as adenovirus 5, in which RNA of S protein is introduced to make the vaccine. In phase 1 human safety trial, no serious adverse reactions were observed in either low-, medium-, or high-dose schedule. The neutralizing antibody level was also found to be high in vaccinated subjects. In addition, eight more companies spreading in the USA/Europe and China are in advance stages of human trial. Once the trial reports are peer reviewed and examined by the respective regulatory authorities, the manufacturing process shall begin. Probably, the world shall experience a variety of vaccines against COVID-19 using different technologies in the development of a single vaccine. The world shall possibly witness the availability of the first RNA-based COVID-19 vaccine which shall be a great breakthrough in vaccine development. As per the WHO, none of the vaccine shall be available in the market before the beginning of 2021.
Novavax with financial aid from CEPI is developing a protein subunit vaccine containing full-length SARS CoV2 glycoprotein nanoparticle and an adjuvant. The initial result in animal models is satisfactory and the vaccine is now in stage 2 of human trial.
The inactivated vaccine developed by the Wuhan Institute of Biotechnology, China, is also in advance stage of human trial and the preliminary report shows adequate production of neutralizing antibody which may be sufficient to protect from the disease.
Inovio pharmaceuticals from the USA is developing a DNA vaccine and the preliminary report on mice and guinea pig model showed adequate production of neutralizing antibody and now in advance stage of human trial.
| Vaccine Development in India|| |
There are several institutions including academic/research and vaccine manufacturing companies in India which are in the process of development of COVID-19 vaccine. As per the Indian news media, about 30 candidate vaccines are in development but not been informed to WHO, as they may be in the preliminary conceptual stage. However, four companies are listed in the WHO website that are in the process of advanced stages of development [Table 2]. In addition, Serum Institute of India shall be manufacturing Oxford-based vaccine, as the company being the largest producing vaccine manufacturer in the world has facility for mass production. Bharat Biotech Limited at Hyderabad has three COVID-19 projects at the moment. The first one is in collaboration with Thomas Jefferson University where the platform would be Vero cell rabies vaccine in which spike protein RNA shall be introduced. The second project is in collaboration with the Indian Council of Medical research (National institute of virology Pune) and already in the process of making an inactivated vaccine by the name Covaxin. The third project is with an American company manufacturing flu vaccine (FluGen)/Wisconsin University and in the same platform shall be trying to make a live intranasal vaccine. All the three projects are in the initial preclinical stage. Zydus Cadila company is in the early clinical stage of development of a DNA based as well as replicating viral vector vaccine. Biological Evans Ltd. is in preclinical stage of development of a viral subunit vaccine and Indian immunological with Griffith University is in a very early stage of development of a live attenuated vaccine. All indigenous vaccines would take even longer time to be available in the market.
|Table 2: COVID19 vaccine development in India as per the World health Organization, June 16, 2020|
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| Challenges in Covid-19 Vaccine Development|| |
A vaccine is a biological product consisting of several ingredients, the most important ones are antigen and adjuvants (Potentiates action of antigen). One should remember that no vaccine can provide 100% protective efficacy and any vaccine having >80% efficacy is considered to be a very good vaccine. The efficacy of a vaccine is judged by human trials and finding out the production of protecting level of antibodies. If the process is successful, the vaccine would be known as highly immunogenic and in terms of percentage of the population who develops the critical protective level of antibodies (in case of COVID-19, it is neutralizing antibody). However, this does not translate into effectiveness of the vaccine. The effectiveness of the vaccine is determined by its capability to protect the disease in a community for which several factors play an important role e.g., the utilization of vaccine usage (coverage) in the community and <80% coverage of any vaccine shall not prevent community spread. Besides, there are many other factors like cold chain maintenance, ethnicity, age, high-risk individuals, immune-compromised persons, etc., which are decisive factors for efficacy and effectiveness of a vaccine. Unless the effectiveness data are available, no one can be certain about how well the new vaccine shall behave.
There has been so much hype about the COVID-19 vaccines all over the world that many countries have already pre booked millions of doses of vaccine from the manufacturer even before the final product is made. There are several challenges that need to be answered before we finally adopt any new vaccine including COVID-19.
- Since there are viral mutations occurring in several countries, making a vaccine with the seed virus obtained from one country may not be immunogenic for others
- One of the most talked Oxford vaccines in the animal trial demonstrated that the vaccine is not able to prevent infection but only a serious form of the disease? If it prevents only serious disease, then the vaccine shall be helpful in individual protection from a severe form and not for stopping pandemic
- One must wait for the safety and efficacy in humans even after mass use and post-marketing surveillance, as the real adverse events are established only after an effective surveillance system in a country. Unfortunately, such an effective monitoring system for adverse events following vaccination is not perfect in many developing countries
- It is still not clear whether one or two doses and any booster dose shall be required. The protective neutralizing antibody level which can prevent infection is also not known so far. The duration of immunity of the vaccine shall be again an important challenge which needs answer
- Equitable distribution of the vaccine in most vulnerable and deprived population needs to be identified. The most deprived population may not get the benefit of the vaccine because of cost and other logistics. WHO, Gavi, and CEPI are working in this aspect. AstraZeneca (UK) has already promised 300 million doses of their vaccine free of cost in this fund
- The availability of vaccine for the entire population of the world would be very difficult, and it may take years for the manufacturer to produce the numbers that may be required for pandemic prevention
- Probably even if the vaccine is available commercially, it shall be difficult to prioritize the group who shall be most benefitted by the vaccine.
| Conclusion|| |
A safe and effective vaccine may be available, but the pandemic may be over and the vaccine may lie unused as it had happened during H1N1 (swine flu) pandemic. It is estimated that only 6% of the any vaccine development process become successful. Hence, there may be only a few vaccines available to fight against COVID-19 disease.
Considering all the challenges mentioned above, even if a safe and effective vaccine is available, it may not be possible to obtain the required number of doses, cold chain maintenance, cost, and other logistics of mass vaccination, especially in developing countries like India. With the public sector investing heavily in the development of these vaccines, there are growing calls for universal vaccine accessibility, but nationalistic, geographical, and commercial factors could stand in the way. The vaccine therefore may not be the only panacea for the prevention and stopping of the pandemic if it continues. We might have to follow general hygienic measures including handwashing, wearing mask, cough and sneeze etiquette, and social distancing for some more time before the pandemic of SARS COVID-19 dies its natural death.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]