A year back on December 31, 2019, China has reported pneumonia-like cases in Huanan Seafood Wholesale Market in Wuhan, Hubei Province. Chinese media on January 11, 2020, reported the first death due to the virus infection. On the next day, based on Next-generation sequencing results, Chinese authorities confirmed that the virus cluster is associated with coronavirus and termed this novel strain as a ‘severe acute respiratory syndrome coronavirus-2’ (SARS-CoV-2), also known as a COVID-19.
The World Health Organisation (WHO) had declared a coronavirus outbreak as a Public Health Emergency of International Concern on 30 January 2020, by then at least 21 countries had reported having COVID-19 positive cases. Over time, more countries started reporting positive COVID-19 cases, seeing the situation, WHO declared COVID-19 as a pandemic on 11thMarch 2020. However, Taiwan has accused WHO of failing to pass the early warning to the other countries regarding virus human-to-human transmission. Taiwan health officials said that they have reported to the WHO, on December 31, 2019 only, that they heard from their colleagues about some kind of dangerous infection spread over mainland China and people there are getting ill.
The deadly coronavirus has reached all seven continents, and as of today, the total cases have reached the mark above 85 million and took the lives of almost 18.5 million people across the globe. Simultaneously, infected people around the world are recovering too because of the good individual immune responseas well as use of “off-label” or “emergency use” drug includes Hydroxychloroquine, Remdesivir, Favipiravir, Dexamethasone, Itolizumab, Tocilizumab, and plasma therapy has shown an effect. But, comorbidities associated with the COVID-19 patients have put the situation at high risk and the most common prevalence of comorbidities includes hypertension, diabetes, cardiovascular disease, and respiratory disease. Here, in this unprecedented time, vaccines, or any kind of targeted therapy has become a priority for every government in the world.
A race against time
From the pre-clinical stage to reach the market, a vaccine development process usually takes 10-15 years. But it is a great moment for the world and science when the COVID-19 vaccine frontrunners have developed vaccines within a year and clinical trial data finds the vaccines are safe and highly effective against SARS-CoV-2. The vaccine developed by the Pfizer/BioNTech, Moderna, and University of Oxford/AstraZeneca has reported their initial efficacy of 95%, 94.5%, and 70% respectively. Unlike previous global virus outbreaks, COVID-19 vaccine development is among the fastest process in which clinical trial has had begun just after two months after the first case was reported. Whereas, the Ebola vaccine reached the public after 5 years of the outbreak while vaccines for other SARS variants, Middle East respiratory syndrome-related coronavirus (MERS), and Zika are still going through clinical trials and development.
If we look the some of the key reasons for the quick COVID-19 vaccine development process are (1) Pool of scientists, researchers, and doctors from worldwide working together against the same target, (2) Availability of advanced technologies to carry out the precise experiments with the highest accuracy, (3) Availability of genome sequencing data of earlier SARS-CoV-1, other deadly viruses followed by SARS-CoV-2 (4) Existing in-depth mRNA, recombinant DNA technology and virus vector research understanding, (4) Sufficient funding (5) Vaccine development process has overcome the several regulatory bottlenecks through progressive collaboration among different governments and regulators to carry out exhaustive clinical trials with diverse patient pool.
A new era of vaccine technology
Interestingly, this is a kind of first mRNA vaccine that got approval for clinical trials and inoculation. The messenger Ribonucleic Acid (mRNA) vaccines contain nucleic acid material, upon injecting into the upper arm, mRNA enters the muscle cells and initiates the process of harmless Spike (S) protein synthesis which resembles the SARS-CoV-2 surface protein. The body’s immune system recognizes these spike proteins as foreign components and elicits an immune response against them which means antibodies will be generated to neutralize the virus. Although COVID-19 mRNA vaccines have emerged as an effective weapon but the technology is not very new, it has been well researched before against flu, Rabies, Zika, Cytomegalovirus (CMV), and Cancers. Technically, mRNA vaccine consists of an open reading frame (ORF) for the target antigen, flanked by untranslated regions (UTRs) and with a terminal poly(A) tail. After an introduction into the cells, they carry out transient antigen expression.
The stability and translation of mRNA are pivotal for the success of any RNA vaccine. Therefore, smart packaging into the small particles helps the mRNA to remain stable, avoid degradation, and achieves targeted delivery to the site of action.Both mRNA vaccines have used a kind of polyethylene glycol (PEG) lipid-based nanoparticle delivery system.
Recently, severe allergy-like reactions were reported after Pfizer/BioNTech injection, and then the packaging material, PEG comes under investigation. Well, the National Institute of Allergy and Infectious Diseases (NIAID), U.S. has recommended not to inject, the currently approved mRNA vaccines to those with a history of a severe allergic reaction to any component of the vaccine. Also, people with a high risk of an anaphylactic reaction should stay at the vaccination site for 30 minutes after their shot so they can be treated if necessary.
On the other hand, the misinformation started spreading that mRNA vaccines are going to alter the human DNA, the scientists have deliberately rejected such rumors. Importantly, mRNA vaccine constituents do not integrate with the host genome and can get degraded naturally during the antigen presentation events.
Meanwhile, other types of vaccines are mainly live-attenuated virus, inactivated virus, or its components whose antigen structure remains intact but devoid of pathogenicity. Such organism-based vaccines have made a huge success in disease control and eradication including polio, smallpox, measles, mumps, and rubella. If we analyze the University of Oxford/AstraZeneca vaccine and Sputnik 5 vaccine, basically it is a weakened version of a common cold virus, an adenovirus construct containing a full‐length coding sequence of SARS-CoV-2 spike protein. The modification in this strain of adenovirus has diminished its replication properties. The construct serves as a suitable vector to carry and deliver a spike protein sequence into the human cells through the angiotensin-converting enzyme-2(ACE2) receptor.
A vaccine race between nations
The world’s focus has shifted from vaccine development to vaccine doses procurement and distribution. The drug makers have started applying for an Emergency Use Authorization (EUA) to the different countries. The United Kingdom(UK) became the first nation who approved the Pfizer/BioNTech BNT162b1 vaccine while closely evaluating the University of Oxford/AstraZeneca vaccine safety and efficacy. While United State of America (USA) who recorded highest deaths due to coronavirus in the world has on December 11, 2020, cleared the first vaccineof Pfizer/BioNTech BNT162b1 by the United State Food and Drug Administration (FDA)for emergency use in the U.S. Surprisingly, just after one week,on December 18, 2020,FDA has authorized second vaccine,ModernamRNA-1273 for emergency use. Countries such as Bahrain, Canada, Saudi Arabia, Israel, Italy, Germany, and Mexico also approved Pfizer/BioNTech BNT162b1 vaccine and a vaccination drive will begin soon. Following others, the European Union approved Pfizer/BioNTech BNT162b1 for emergency use. New Zealand will soon begin their vaccination campaign with the AstraZeneca and Novavax vaccine. However, the World’s most populated country where the first coronavirus case was also reported, China, has already begun inoculating its home-grown experimental vaccines in several Chinese cities. Another South-Asian giant and second highest populated country, India have received three vaccines EUA application, the Central Drug Standard Control Organisation (CDSCO) of the Government of India, is scrutinizing the applications.
The application filed by (1) Serum Institute of India (SII) with University of Oxford/AstraZeneca vaccine COVIDSHIELD, (2) Bharat Biotech, in collaboration with National Institute of Virology-Indian Council of Medical Research (ICMR) vaccine Covaxin, and (3) Pfizer/BioNTech BNT162b1. However, on January 1, 2021, the Indian government approved the University of Oxford/AstraZeneca/Serum Institute of India, vaccine, COVISHIELD for immunization while on the next day January 2, 2021, India’s indigenously developed Covaxin got the nod for restricted emergency-use.
After conducting two dry run of vaccine across the country, Indian government announced the vaccination to be started from January 16, 2021 for around 30 million people in the first phase which consists of health workers, frontline corona warriors, aged citizens (above 50yrs), and coronavirus infected patients with serious commodities. An Application Programming Interface named CoWIN (COVID Vaccine Intelligence Work), a digital platform will be there to support and to strengthen the whole vaccination distribution system (VDS).
Here, the data shows which categories of countries are securing the vaccine doses for their citizens. It can be seen that the high-income countries are acquiring most of the vaccines of different types. Unfortunately, most of these high-income countries have only recorded the highest deaths and still, their COVID-19 cases are surging.
The country income level classification is based on the estimated number of doses purchased. The information was accessed on 30th December 2020, from the Duke Global Health Innovation Center website.
Well, it was being predicted very early that only vaccine development against coronavirus will not be enough. Along with vaccine development, fair distribution needs to be ensured. The early agreement with pharmaceutical companies and the pre-booking of the vaccine by several rich nations has triggered the issue of vaccine nationalism. Not every country is self-sufficient in vaccine production. After all, such attempts of pre-booking likely to make vaccines unavailable in a necessary amount to the low income or poor countries.
This “me-first” approach by the rich countries, has led to the demand for the formation of a platform whose objective will be development, production, and equitable access of COVID-19 vaccine for low-income and poor countries. And then, COVAX, The COVID-19 Vaccines Global Access Facility under the ACT (or Access to COVID19 Tools) Accelerator Programme, was launched to serve the purpose. COVAX is co-led by Gavi, the Coalition for Epidemic Preparedness Innovations (CEPI),and the WHO. Gavi, a public-private partnership, vaccinates children against deadly diseases around the world. COVAX has raised US$700 million toward an initial target of $2 billion funds, while secured 400 million of the 2 billion doses target, procurement and distribution by the end of 2021 to support the 92 countries eligible for the Gavi COVAX AMC (advance market commitment) that will be covered up to 20% population. The agenda is to negotiate with the pharmaceutical companies to produce vaccines at a reasonable price. Unlike, other vaccine developers, AstraZeneca has pledged to not make a profit on the vaccine during the pandemic and has reached agreements with governments and health organizations.
This race is long since several roadblocks and milestones are there to reach the final destination.
1) How long the vaccine shots will keep the individual protective from virus attack? Since there is no sure shot answers are available. Still, the experts believe that it will be effective over the next six months to a year, and by then the body could develop specific immunity and the ability to produce neutralizing antibodies against coronavirus. Technically, to a certain extent, it can be expected that the person won’t get re-infected after a year. 2) Do the approved vaccine will be effective against the newly SARS-CoV-2 mutated strains? First of all, we need to understand that mutation in any virus is a natural event unless it mutates in a way that can cause any detrimental effect further. Now, the mutation observed in SARS-CoV-2 in the genes which encodes the spike protein using which virus enters human cells. The SARS-CoV-2 mutated variant found in the UK has 14 mutations that cause a change in protein building blocks (amino acids) and three deletions (missing bits of genetic code). However, the CDC and vaccine developers anticipate that vaccines will work against coronavirus new mutated strain.
3) How to deal with rumors, misinformation, and conspiracy theories around the vaccine.
There is no doubt that with the beginning of the pandemic, an anti-vaccine campaign is fueled by an amalgam of players, some who don’t believe any politicians, others who run any anti-government propaganda, and many who believe misinformation and conspiracy theories about vaccines. This time, anti-vaxxers have mainly targetedsocial media platforms. Therefore, especially, India needs to be more vigilant.
A vaccine work is to trigger the body’s immune system & immunity is everything in the fight against the coronavirus. The factors which could have an influence on vaccine effect are age, sex, genetics, and comorbidities, in addition, vaccine type, product, adjuvant, and doses too.
Disclaimer: The figures are being created based on the information gathered by the author exclusively for this article. Anyone who wants to use these figures specifically, the user must cite the article in their reference.
The views and opinions are the author’s personal. Saurabh Mandal is a 4thyear Ph.D. student at Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education, Bangalore, Karnataka, India.