|Year : 2021 | Volume
| Issue : 2 | Page : 111-121
The COVID-19 vaccine: A race nearing the finish line
Tarun Kumar Suvvari1, Siddhi Hegde2, Shreya Sreeram2, LV Simhachalam Kutikuppala3
1 Rangaraya Medical College, Kakinada, Andhra Pradesh, India
2 KVG Medical College and Hospital, Sullia, Karnataka, India
3 Konaseema Institute of Medical Sciences and Research Foundation, Amalapuram, Andhra Pradesh, India
|Date of Submission||02-Mar-2021|
|Date of Decision||20-Mar-2021|
|Date of Acceptance||31-Mar-2021|
|Date of Web Publication||25-May-2021|
L V Simhachalam Kutikuppala
Konaseema Institute of Medical Sciences and Research Foundation, Amalapuram, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
The impact of the coronavirus disease-2019 (COVID-19) pandemic on global health and the economy is so extensive that it has driven several countries to go on a quest for a vaccine. The evaluation of future generation vaccine platforms is the need of the hour. In the majority of nations, innovative technology is being used to hasten the vaccine development process. The evolution of a safe and effective vaccine takes time. The journey from its genesis to making the final product available to the public is a tedious course of action. Vaccines generally function by mimicking the infectious agent, which can be a bacterium, virus, or other microorganisms that cause disease. The characteristic feature of the COVID-19 vaccine development is the use of a wide array of technology platforms, including the virus-like particle, peptide, nucleic acid (DNA and RNA), viral vector (replicating and nonreplicating), live attenuated virus, an inactivated virus, and recombinant protein in the process of vaccine preparation. Despite the hurried nature of their current development, all COVID-19 vaccines being developed will receive regulatory approval only if they meet the rigorous safety and efficacy standards. Effective and productive global co-ordination and co-operation between the vaccine developing agencies, regulating authorities, policymakers, governments, funding organizations, and public health bodies are essential to ensure the large-scale manufacturing and equitable distribution of promising end-stage vaccine candidates. Besides various concerns on the safety and efficacy of various COVID-19 vaccines, the vaccination drive had successfully started in most developed and developing countries in the global race to vaccinate the people.
Keywords: Coronavirus disease-2019, efficacy, pandemic, severe acute respiratory syndrome coronavirus 2, vaccine
|How to cite this article:|
Suvvari TK, Hegde S, Sreeram S, Simhachalam Kutikuppala L V. The COVID-19 vaccine: A race nearing the finish line. Apollo Med 2021;18:111-21
| Introduction|| |
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), reported first in China, is the causative agent of the coronavirus disease-2019 (COVID-19) pandemic. To alleviate the terrible effects of this current pandemic on our public health, the economy, and society, the development of an effective and safe vaccine is crucial. This COVID-19 pandemic, which is essentially the most devastating pandemic of the century, demands a rapid assessment and proactive steps to elicit protective immunity and safety to curtail unwanted immunopotentiation salient feature of the pathogenesis of this virus. A vaccine is a product that stimulates a person's immune system to produce immune cells against a specific disease, serving as a means of prevention. Vaccines are miracle tools that can train our body to wage an attack on a specific pathogen. However, the question arises as to how introduction of a pathogen can provide protection against a disease. The answer is simple; the antigens in the vaccines produce a primary immune response that consists of T and B memory cells specific to that antigen. Furthermore, upon future infection by the same pathogen, an immune response ensues. The discovery of vaccines has been the most illustrious tool in modern medical science.
After years of studies and development, various vaccine types are still being contrived. The current types of vaccines include live pathogens (varicella, mumps, and measles), inactivated pathogens (rabies and hepatitis A), acellular or subunit (influenza), conjugated polysaccharides (H. influenza and pneumoccoci), and recombinant subunit (hepatitis B virus and human papillomavirus). Due to the diverse nature of pathogen virulence, humankind has to toil hard to find newer ways to fight them. The novel vaccine types such as viral vectors and nucleic acid (DNA and RNA) vaccines have already developed and currently are in use. They pose as proof of advancing techniques in vaccine research and development.
Properties of an ideal COVID-19 vaccine:
- Excellent safety profile across different age groups and populations
- No or few contraindications
- Minimal adverse events that are mild and of short duration
- Induce protective immunity – ideally after a single dose and gives rapid protective immunity
- At least 70% efficacy
- Protection in health-care workers who face high-titer virus exposure
- Long-lasting protection involving both humoral and cell-mediated responses
- If booster doses are required, not more frequent than yearly
- Rapid mass production, stable at room temperature, easy administration, and which can be co-administered with other vaccines.
| Role of Spike Proteins in Coronavirus Disease-2019 Vaccines|| |
Based on past studies of SARS-CoV, MERS-CoV, and SARS-CoV-2, it is found that the S-protein plays a key role in virus–host interaction and enters into human cells. These proteins are vital to the ultimate success of vaccines and therapeutics. Many neutralizing antibodies have been found against the previous viruses. These antibodies however have very limited efficacy. Most of the previous vaccines/neutralizing antibodies led to antibody-dependent enhancements (ADE) as fewer antibodies were generated due to vaccines.
The vaccines/neutralizing antibodies must be effective on different strains of SARS-CoV-2 across the globe. Nanobodies were found to have successfully prevented the ADE effect. Recently, it was found that D614 G mutation was present in the viral spike protein, which was dominating in many countries. It can lead to severe COVID-19 diseases with a higher infectivity. However, the vaccines currently being developed have shown a significant positive effect on that strain too. Cross-challenging studies in vaccinated animals using new strains are needed to evaluate vaccines' efficacy along with safety.
| Current Scenario of Coronavirus Disease-2019 Vaccines Across the Globe|| |
The Vaccines that have been approved for the emergency human administration by WHO were Pfizer & BioNTech, Moderna, AstraZeneca/ University of Oxford. Many more vaccines are in the race heading toward market approval.,,, A comprehensive list of vaccines and their research and development till date is represented in [Table 1].,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,, On December 2, 2020, the United kingdom (UK) became the first country to approve the COVID-19 vaccine in the world and vaccination is set to start from next week for the UK population.
| Coronavirus Disease-2019 Vaccine and Bioethics|| |
Vaccine development is a lengthy and rigorous process that usually requires several years to move from the preclinical setup, including in vitro and animal testing, to the clinical trials and then to the large-scale vaccine production and finally the licensing part. Safety of the vaccine is a critical part, which must be confirmed by extensive preclinical and safety trials, followed by inoculation of a significant number of humans, exponentially expanding to thousands of the population to prove its efficacy and safety.
Ethical conduct is of utmost importance to avoid exploitation of resources and to validate the scientific knowledge being used. The substantiation of partnership and association with the researchers, experts, and officials from the affected countries as well as transparency of independent review systems and scientific supervision is vital. These are basic bioethical principles that need to be practiced to conduct trials in this global emergency of the COVID-19 pandemic. The interrelation between these principles should be noted, as the local realities and pressures can complicate equitable distribution. A diplomatic invitation is an extremely useful and essential step in government-to-government partnerships. The critical evaluation of a country's capacity in conducting clinical research must be well addressed. The regulatory monitoring for all bioethical practices needs to be strengthened. The urgency in defining the priority and objectives of these studies needs to be superscribed well. The Institutional Review Boards (IRBs) and Ethics Committees (E. Cs) play a crucial role in vaccine development in maintaining the standards from the beginning. Being faced with an unprecedented pandemic with a heavy focus on scientific research, the IRBs and E. Cs must foresee the conduct of the study closely and strictly, constantly assessing the inputs and outputs for guaranteeing and safeguarding the participant's safety.
| Vaccination Drive and India|| |
On January 16, 2021, India has initiated the world's largest COVID-19 vaccination drive with 3006 vaccination centers across India. The frontline workers were given first preference, followed by people who are over 60 years of age and people with 45 years and above age with specified comorbid conditions., From April 1, 2021, all citizens aged 45 years and above age were made eligible to get vaccinated. By March 22, 2021, the COVID-19 vaccination drive in India has reached 65 days, during which we have been able to vaccinate 3.75 crore beneficiaries, of which 75 lakh people have completed the two-dose vaccine schedule successfully as per the National Expert Group on Vaccine Administration for COVID-19 (NEGVAC) guidelines. In the view of emerging scientific evidence, the interval between the two doses of a specific COVID-19 vaccine, i.e., COVISHIELD has been revised by the National Technical Advisory Group on Immunization in India and NEGVAC to provide the second dose of COVISHIELD at 4–8 weeks interval after first dose.
The total number of vaccination doses administrated per 100 people in the total world population is depicted in [Figure 1]. By March 23, 2021, a total of 3% of the Indian population has received the first dose and 0.6% have received the second dose [Figure 2]. Ladakh tops the list with 13.3% received first dose and 2% received second dose.
|Figure 1: COVID-19 vaccine doses administered per 100 people (worldwide)|
Click here to view
|Figure 2: Percentage of Indian population received 1first and second dose by March 23, 2021|
Click here to view
There is an average waste of 6.5% vaccine wastage across India, and the center urged states to minimize waste as now vaccines are invaluable commodities. Vaccines are public health things, and therefore, they have to be optimally utilized. The sudden rise in COVID-19-positive cases has shown a significant impact on India's movement to vaccinate its 1.3 billion people against COVID-19. Until now, nearly 40 million people only received one dose of vaccine. With this current vaccination rate, it would take a decade to vaccinate 70% of the Indian population., People's knowledge and attitude toward COVID-19 and vaccines will also play a key role in vaccination drive. The fact is that people's decision to get vaccinated is multifactorial and is subjected to change over time.
| Discussion|| |
Many drugs and vaccines for the management of COVID-19 were in the pipeline around the globe. However, vaccines have a remarkable impact on COVID-19 control and minimize its effect on people.,,, Our current understanding of immunity following natural COVID-19 infection, primarily based on the experience with previous SARS-CoV and MERS infections, showed that protective immunoglobulin G antibodies rise after virus infection. After 3–4 months, their levels go down to a certain level which is usually detectable up to 2 years, (Titers known to protect against COVID-19 infection still remain unknown). Specific T-cell immunity which is equally important has been shown to persist even up to 17 years. This simply means, in COVID-19, possible recurrence of infection is an exception (very rare) but not a rule. Therefore, till now, out of millions of infections, only a few cases (<100) have been reported to have re-infection and none of them were severe infection.
We can expect vaccine immunity to follow similar rules, set by natural infection with COVID-19. Based on R0 of SARS-CoV-2, at least 70% of our population need to get immunity either by natural infection or by vaccination. Until this figure of 70% immunity is crossed, infection is unlikely to stop. Recent Indian Council of Medical Research seroprevalence study from India representing a wider population from various parts of the country (before vaccination started) has shown the presence of protective antibodies in 35%–40% of population in major cities and 10%–20% in rural areas., Since the target is not to achieve 70% of immunity in population (unless we could vaccinate the whole population, almost an impossible task), the focus needs to be to protect the vulnerable from hospitalization and death, i.e., above 60 and 45–60 years with comorbidities.
There is a need to urgently rework the vaccination strategy and encourage “vaccination on demand” to eligible people, high-risk people, frontline workers in all fields, and those interacting with large numbers every day and exposed to the risk of infection. Fortunately, India has more than adequate vaccine production capacity, involving private health sector may increase the reach of vaccination and decrease vaccine hesitancy. Allowing companies, organizations, firms…etc., to vaccinate their workforce can be implemented. Many districts in India have nearly 60% cases. Massive vaccination drive should be undertaken in these districts in a mission mode. Instead of generalized lockdowns, speedy massive vaccination along with effective disease surveillance should be urgently implemented.
| Conclusion|| |
The whole world has waited for the COVID-19 vaccines with bated breath, besides various concerns on safety and efficacy of various COVID-19 vaccines, in the global race to vaccinate the people, the vaccination drive had successfully started in most of the developed and developing countries. These vaccines promise the concept of herd immunity to groups of people who are particularly vulnerable due to chronic diseases, such as people with advanced age and those with comorbidities. COVID-19 vaccines will have an important role in preventing and controlling the pandemic and also on herd immunity if these vaccines have sustainable efficacy in reducing morbidity and mortality among high-risk groups. Global health agencies must communicate with policymakers and the general public that these vaccines could be a major tool for the comprehensive public health response toward COVID-19. Vaccination is the key to control COVID-19. The only way to prevent the disease so far is social norms and vaccines.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Krammer F. SARS-CoV-2 vaccines in development. Nature 2020;586:516-27.
Kaur SP, Gupta V. COVID-19 vaccine: A comprehensive status report. Virus Res 2020;288:198114.
Garçon N, Leroux-Roels G, Cheng W. Understanding Modern Vaccines: Perspectives in Vaccinology. Elsevier; 2011.
Baxter D. Active and passive immunity, vaccine types, excipients and licensing. Occup Med (Lond) 2007;57:552-6.
Haynes BF, Corey L, Fernandes P, Gilbert PB, Hotez PJ, Rao S, et al
. Prospects for a safe COVID-19 vaccine. Sci Transl Med 2020;12:eabe0948.
Samrat SK, Tharappel AM, Li Z, Li H. Prospect of SARS-CoV-2 spike protein: Potential role in vaccine and therapeutic development. Virus Res 2020;288:198141.
Yanjun Zhang, Gang Zeng, Hongxing Pan, Changgui Li, Biao Kan, Yaling Hu et al
. Immunogenicity 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 2020.07.31.20161216. [doi: 10.1101/2020.07.31.20161216].
Walsh EE, Frenck RW Jr., Falsey AR, Kitchin N, Absalon J, Gurtman A, et al
. Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates. N Engl J Med 2020;383:2439-50.
Mulligan MJ, Lyke KE, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al
. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature 2020;586:589-93.
Annette B. Vogel, Isis Kanevsky, Ye Che, Kena A. Swanson, Alexander Muik, Mathias Vormehr et al.
A prefusion SARS-CoV-2 spike RNA vaccine is highly immunogenic and prevents lung infection in non-human primates. bioRxiv 2020.09.08.280818. [doi: 10.1101/2020.09.08.280818].
Jackson L, Anderson E, Rouphael N, Roberts PC, Makhene M, Coler RN, et al
. An mRNA Vaccine against SARS-CoV-2 – Preliminary report. N Engl J Med 2020;383:1920-31.
Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, et al
. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med 2020;383:2427-38.
Corbett KS, Flynn B, Foulds KE, Francica JR, Boyoglu-Barnum S, Werner AP, et al
. Evaluation of the mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates. N Engl J Med 2020;383:1544-55.
Corbett KS, Edwards DK, Leist SR, Abiona OM, Boyoglu-Barnum S, Gillespie RA, et al
. SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness. Nature 2020;586:567-71.
Kremsner P, Mann P, Bosch J, Fendel R, Julian J. Gabor, Kreidenweiss A, et al.
Phase 1 assessment of the safety and immunogenicity of an mRNA- lipid nanoparticle vaccine candidate against SARS-CoV-2 in human volunteers. medRxiv 2020;11:09.20228551. [doi: 10.1101/2020.11.09.20228551].
Xia S, Zhang Y, Wang Y, Wang H, Yang Y, Gao GF, et al
. Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: A randomised, double-blind, placebo-controlled, phase ½ trial. Lancet Infect Dis 2021;21:39-51.
Xia S, Duan K, Zhang Y, Zhao D, Zhang H, Xie Z, et al
. Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes. JAMA 2020;324:951-60.
Yadav PD, Ella R, Kumar S, Patil DR, Mohandas S, Shete AM et al
. Immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidate, BBV152 in rhesus macaques. Nat Commun. 2021;12:1386. doi: 10.1038/s41467-021-21639-w.
Zhu F, Guan X, Li Y, Huang JY, Jiang T, Hou LH, et al
. Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older: A randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 2020;396:479-88.
Logunov DY, Dolzhikova IV, Zubkova OV, Tukhvatulin AI, Shcheblyakov DV, Dzharullaeva AS, et al
. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: Two open, non-randomised phase ½ studies from Russia. Lancet 2020;396:887-97.
Sadoff J, Le Gars M, Shukarev G, Heerwegh D, Truyers C, de Groot AM et al
. Interim Results of a Phase 1-2a Trial of Ad26.COV2.S Covid-19 Vaccine. N Engl J Med. 2021:NEJMoa2034201. doi: 10.1056/NEJMoa2034201.
A Study Looking at the Effectiveness, Immune Response, and Safety of a COVID-19 Vaccine in Adults in the United Kingdom – Full Text View – ClinicalTrials.gov. Clinicaltrials.gov; 2020. Available from: https://clinicaltrials.gov/ct2/show/NCT04583995
. [Last accessed on 2020 Nov 27].
Keech C, Albert G, Cho I, Robertson A, Reed P, Neal S, et al
. Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine. N Engl J Med 2020;383:2320-32.
Huang B, Dai L, Wang H, Hu Z, Yang X, Tan W, et al
. Neutralization of SARS-CoV-2 VOC 501Y.V2 by human antisera elicited by both inactivated BBIBP-CorV and recombinant dimeric RBD ZF2001 vaccines. bioRxiv 2021;02.01.429069. [doi: 10.1101/2021.02.01.429069].
Ospina Henao S, Marín Mora A, Chan Solano F, Ávila-Aguero ML. Bioethical implications in vaccine development, a COVID-19 challenge. Cureus 2020;12:e10530.
Vercler C. Navigating the ethical Scylla and Charybdis of the COVID vaccine. J Pediatr Rehabil Med 2020;13:229-31.
Lane HC, Martson HD, Fauci AS. Conducting clinical trials in outbreak settings: Points to consider. Clin Trials 2016;13:92-5.
Shah SK, Miller FG, Darton TC, Duenas D, Emerson C, Lynch HF et al
. Ethics of controlled human infection to address COVID-19. High social value is fundamental to justifying these studies. AAAS 2020;368:832-4.
Kutikuppala LV, Kiran AN, Suvvari TK. Knowledge, attitude, and practices toward the COVID-19 pandemic among the Indian general population: A cross-sectional survey. Indian J Respir Care 2021;10:88-92. [Full text]
Burugu HR, Kandi V, Kutikuppala LV, Suvvari TK. Activities of serum ferritin and treatment outcomes among COVID-19 patients treated with vitamin C and dexamethasone: An uncontrolled single-center observational study. Cureus 2020;12:e11442.
Suvvari TK. Therapeutic uses of monoclonal antibodies for COVID-19. Biomed Res J 2020;7:60-1. [Full text]
Edara L, Suvvari TK, Kutikuppala LV. High dose steroid therapy to prevent severe hypoxia in COVID-19 patients: A potential solution for low resource clinical setting. Cureus 2020;12:e12330.
Suvvari TK, Simhachalam Kutikuppala LV, Babu GK, Jadhav M. Understanding the unusual viral outbreak: Coronavirus disease 2019. J Curr Res Sci Med 2020;6:3-10. [Full text]
Chia WN, Zhu F, Ong SW, Young BE, Fong SW, Le Bert N, et al
. Dynamics of SARS-CoV-2 neutralising antibody responses and duration of immunity: A longitudinal study. Lancet Microbe 2021;Published Ahead of Print [doi: 10.1016/S2666-5247 (21) 00025-2].
Murhekar MV, Bhatnagar T, Selvaraju S, Rade K, Saravanakumar V, Vivian Thangaraj JW, et al
. Prevalence of SARS-CoV-2 infection in India: Findings from the national serosurvey, May-June 2020. Indian J Med Res 2020;152:48-60.
] [Full text]
[Figure 1], [Figure 2]