Articles

Recent Advancement In COVID-19 Vaccine And Their Role In Controlling Spread Of Corona Virus Pandemic

Author: Dr. Shiju John

M.B.B.S, MD (General Medicine), DM (Gatroenterology) Bishop Benziger Hospital, Kollam

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Abstract

Recent spread of SARS-CoV-2 pandemic has caused many casualties. Many measures to control the spread are based on prevention and symptomatic treatment. Apart from many attempts in finding the cure, there is still no approved medicine which can cure this deadly viral infection. The most promising options the vaccine, which helps in developing immunity against the infection from SARS-CoV-2. Various researches are going on for development of potent vaccines and are evaluated clinically for their efficacy.

Keywords: SARS-CoV-2 pandemic, COVID-19 vaccine, Treating coronavirus.

 

Introduction

Coronavirus disease 2019 (COVID-19) has spread globally at a rapid pace since the novel coronavirus was first reported in late December 2019 in Wuhan, China, and was declared a pandemic by the World Health Organization on March 11, 2020 [1]. COVID-19 disease caused by the SARS-CoV-2 virus spreads from country to country, following modern travel routes [2]. A demographic study in late December of 2019 showed that the percentages of the symptoms were 98% for fever, 76% for dry cough, 55% for dyspnoea, and 3% for diarrhoea; 8% of the patients required ventilation support [3]. The diagnosis of SARS-CoV-2 infection is achieved through detection of viral RNA from a nasal pharyngeal swab or saliva, by nucleic acid tests (NATs) or tests that detect viral protein antigens. In infected individuals, the results are only positive for a relatively short time window, on average until the 14th day after symptom onset [4-5].

Contact tracing is a core public health intervention that plays an important role in the control of COVID-19 [6].

The aim of contact tracing is to rapidly identify potentially newly infected persons who may have come into contact with existing cases, in order to reduce further onward transmission. Contact tracing consists of three steps [7] (figure 1):

• Contact identification: To identify persons who may have been exposed to SARS-CoV-2 as a result of being in contact with an infected person.
• Contact listing: To trace and communicate with the identified contacts and to provide information about suitable infection control measures, symptom monitoring and other precautionary measures such as the need for quarantine.
• Contact follow-up: To monitor the contacts regularly for symptoms.

 

Figure 1: Contact tracing protocol

 

Treatment Options

Therapeutic options for coronavirus disease 2019 are desperately needed to respond to the ongoing SARS-CoV-2 pandemic. Various researches are going on for finding the cure; meanwhile many potential medicines are being used for managing the symptoms and viral load in infected patients. Both antiviral drugs and immunomodulators might have their place in the management of coronavirus disease 2019 (table 1). Unfortunately, no drugs have been approved yet to treat infections with human coronaviruses [8].

• Antivirals: Various antiviral agents with apparent in vitro activity against SARS-CoV and MERS-CoV were used during the SARS and MERS outbreaks, with inconsistent efficacy [9] and are also being considered for SARS-CoV-2.
• Corticosteroids: The rationale for the use of corticosteroids is to decrease the host inflammatory responses in the lungs, which may lead to acute lung injury and acute respiratory distress syndrome (ARDS) [10]. Observational studies in patients with SARS and MERS reported no associations of corticosteroids with improved survival, but demonstrated an association with delayed viral clearance from the respiratory tract and blood and high rates of complications including hyperglycaemia, psychosis, and a vascular necrosis [11].
• Immunomodulators: Monoclonal antibodies directed against key inflammatory cytokines or other aspects of the innate immune response represent another potential class of adjunctive therapies for COVID-19. The rationale for their use is that the underlying pathophysiology of significant organ damage in the lungs and other organs is caused by an amplified immune response and cytokine release, or “cytokine storm” [12].
• Plasma Therapy: Convalescent plasma (CP) has been used successfully to treat many types of infectious disease, and has shown initial effects in the treatment of the emerging SARS-CoV-2. CP therapy is a form of passive immunization in which antibody-rich blood is collected from recovered patients and then processed to transfuse into infected patients. As of now, it is a potentially effective treatment for COVID-19 [13].

 

Table 1: Therapeutic options considered for treating SARS-CoV-2

Therapeutic considerations for COVID-19 management
Antiviral	Anti-inflammatory	Convalescent Plasma
Remdesivir Favipiravir Lopinavir – Ritonavir Ribavirin Chloroquine and Hydroxychloroquine	Glucocorticoids Tocilizumab Siltuximab		Serum-containing neutralizing antibodies

 

Vaccines

Vaccination is the best way to prevent an infectious disease, the development of an effective vaccine against SARS-CoV-2 can not only reduce the morbidity and mortality associated with it, but can also lessen the economic impact.

It is estimated that 60–70% of a population would need to be immune to achieve herd immunity against SARS-CoV-2. The safest and most controlled way for effective and sustainable prevention of COVID-19 in a population is to have an efficacious and safe vaccine and the majority of the population successfully vaccinated [14].

Researching of vaccines has to faces multiple challenges during its development. Traditional way of development is a time taking process. So in times of emergency pandemics the process needs to be accelerated for early development of cure (figure 2). This has led to the modified approach towards development of vaccine with many phases going on simultaneously [15].

Figure 2: Various phases of vaccine development (traditional and accelerated) with timeline.

 

Development of Vaccine

Different measures for development of vaccine are considered, this leads to many types of vaccines to be considered for manufacturing process.

Live-Attenuated Vaccines

Live attenuated vaccine (LAV) is the most immunogenic vaccines that do not require adjuvant to gain optimal response due to its effectiveness to provoke immunity mimic to the natural infection [16]. Several LAVs are found in the market to protect various disease including mumps, rubella, measles and varicella vaccines. LAV is not suitable for infants, immune-compromised patients, and elderly people due to the risk of reversion to virulent strain [17]. Codagenix Biotec Inc collaboration with the Serum Institute of India Ltd developing a live-attenuated SARS-CoV-2 vaccine in which the sequence of the target gene of interest has been changed by swapping its optimized codons with non-optimized ones [18].

Inactivated Whole-Virus Vaccine

Inactivated whole-virus comprises the entire disease-causing virion which is inactivated physically (heat) or chemically. It has several antigenic parts to the host and can induce diverse immunologic responses against the pathogen [19]. IWV is conventional vaccines with mature technology and may become the first SARS-CoV-2 vaccine put into clinical use. There are three inactivated whole-virus vaccines against SARS-CoV-2 reached phase 1/2 clinical trial. These phase 1/2 clinical trials are done by the Beijing Institute of Biological Products, Sinovac and Wuhan Institute of Biological Products [20].

Subunit Vaccines

Subunit vaccines contain pathogen-derived proteins (antigens) with immunogenicity that can elicit the host immune system. Subunit vaccine is safe and easily manufactured by recombinant DNA techniques but requires adjuvant to enhance an immune response [21].

Novavax, Inc. developed a candidate vaccine based on S protein. So far, Clover Biopharmaceuticals constructed a SARS-CoV-2 S protein trimer vaccine (S-Trimer) by using its patented Trimer-Tag© technology [22].

mRNA Vaccines

mRNA carries instruction from the protein-encoding DNA to the proteins translating ribosomes. There are two types of mRNA vaccines platform: non- replicating mRNA and self-amplifying mRNA that encodes not only the required antigen but also the viral replication machinery.

mRNA vaccine is a promising alternative to traditional vaccine approaches due to their safety, potency, quick vaccine-development time, and low-cost production. The procedures to develop the mRNA vaccine include the screening of antigens, the optimization of sequences, modified nucleotides screening, delivery systems optimization, evaluation safety, and immune response [23-24].

Duke-NUS Medical School and Arcturus Therapeutics partnered to develop a self-replicating mRNA vaccine candidate, currently in a preclinical trial. BioNTech and Pfizer are collaborating to co-develop mRNA-based vaccine candidate BNT162 [25].

DNA Vaccine

DNA vaccines (DVs) have a plasmid into which a particular gene incorporated that encodes the antigens that identified from the pathogenic microorganism. DVs elicit both the cell-mediated and humoral immune system. DVs induce long-lasting immunity that defends the diseases effectively in the future. DVs are very stable, can be produced within weeks because they do not need culture or fermentation; instead used synthetic processes and began clinical trial within months. Currently, DNA vaccine not approved for the market [26]. Inovio Pharmaceuticals developed a DVs candidate termed INO-4800, which is in phase 1 (NCT04336410) clinical trial. Takis/Applied DNA Sciences/Evvivax and Zydus Cadila are developing a DVs candidate for COVID-19 disease which is now in preclinical studies [27].

 

Viral Vector-Based Vaccine

Viral vector vaccine works by carrying a DNA express or antigen(s) into host cells, thereby eliciting cell-mediated immunity in addition to the humoral immune responses. Viral Vectors Vaccines are characterized by strong immunogenicity and safety [28]. Several viral vectors are available for vaccine development including vaccinia, modified vaccinia virus Ankara (MVA), adenovirus (Ad), adeno-associated virus (AAV), retrovirus/lentivirus, alphavirus, herpes virus, Newcastle disease virus, poxvirus, and others. Viral vectors can be replicating or non-replicating viruses [29].

Currently, Can Sino Biological Inc. and the Beijing Institute of Biotechnology are developing Ad5- vector COVID-19 vaccine candidate in Phase 1(ChiCTR2000030906). Another adenovirus vectored vaccine developed by Chen Wei group entered in phase 1 clinical trial (NCT04313127). Johnson & Johnson is developing an adenovirus vectored vaccine using AdVac®/PER.C6® vaccine platforms. Shenzhen Geno-Immune Medical Institute also developing two lentivirus vector based vaccine candidates named COVID-19/aAPC and LVSMENP- DC [30].

Synthetic Peptide or Epitope Vaccine

Synthetic Peptide vaccines are chemically produced from fragments of antigens that elicit the immune response. These vaccines are inexpensive, easy for preparation, and quality control. But display low immunogenicity, thus antigen modification and adjuvant required during formulation [31].

Several pharmaceutical companies like Generex Biotechnology developing peptide based vaccines against SARS-CoV-2 viruses by producing synthetic peptides that mimic crucial antigens from a virus that is chemically bonded to the 4-amino acid Ii-Key to ensure robust immune system activation [32].

Virus-Like Particles Based Vaccine

Virus-like particles (VLPs) are “hollow-core” virus particles formed by the viral structural component with self-assembly character into nanostructure. VLPs represent advanced subunit vaccine with increased immunogenicity because they contain the structural protein of the virus [33]. VLP-based vaccines produced for greater than 30 different viruses including GlaxoSmithKline's Engerix® (hepatitis B virus) and Cervarix® (human papillomavirus), and Merck and Co., Inc.’s Recombivax HB® (hepatitis B virus) and Gardasil® (human papillomavirus) [34].

 

COVID-19 Vaccines under Development

As of October 2020, there are 42 COVID-19 candidate vaccines in clinical evaluation, of which ten are in Phase III trials. There are another 151 candidate vaccines in preclinical evaluation. Phase III trials which usually require 30,000 or more participants, are undergoing. All top candidate vaccines being considered are given for intra-muscular injection. Most of the developed vaccines are designed for a two-dose schedule (exceptions with asterisk (*) in table 2 are single dose).

Table 2: COVID-19 vaccine candidates in Phase III trials [35]

Candidate Vaccines in Phase III Clinical Evaluation	Vaccine Platform	Location of Phase III Studies
Sinovac	Inactivated virus	Brazil
Wuhan Institute of Biological Products / Sinopharm	Inactivated virus	United Arab Emirates
Beijing Institute of Biological Products /  Sinopharm	Inactivated virus	China
University of Oxford / AstraZeneca	Viral Vector*	United States of America
CanSino Biological Inc./ Beijing Institute of Biotechnology	Viral Vector*	Pakistan
Gamaleya Research Institute	Viral Vector	Russia
Janssen Pharmaceutical Companies	Viral Vector	USA, Brazil, Colombia, Peru, Mexico, Philippines, South Africa
Novavax	Protein subunit	United Kingdom
Moderma / NISID	RNA	USA
BioNTech / Fosun Pharma / Pfizer	RNA	USA, Argentina, Brazil

 

Conclusion

COVID-19 pandemic is increasing on massive scale on day to day basis. Spread of SARS-CoV-2 infection can be avoided by following good social practices and maintaining proper hygiene. The casualties are being controlled by providing the immediate medical attention and treating symptomatically. But for eradicating such a deadly virus a proper cure needs to be discovered.  Many current researches on development of vaccine for COVID-19 is going on and have proceeded for third phase clinical trials. These potential candidate vaccines hold a promising ray of hope against finding a cure for COVID-19.

 

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