key: cord-0689174-gkcan78j
authors: Belete, Tafere Mulaw
title: A review on Promising vaccine development progress for COVID-19 disease
date: 2020-06-13
journal: Vacunas
DOI: 10.1016/j.vacun.2020.05.002
sha: 19c5ec71c94ce42b3b47d169e3d8b86a38641210
doc_id: 689174
cord_uid: gkcan78j

Abstract The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) that causes corona virus disease 2019 (COVID-19) and its impact on in the world have made imperative progress to develop an effective and safe vaccine. Despite several measures undertaken, the spread of this virus is ongoing. So far, more than 1,560,000 cases and 1000,000 deaths occurred in the world. Efforts have been made to develop vaccines against human coronavirus (CoV) infections such as MERS and SARS. However, currently, no approved vaccine exists for these coronavirus strains. Such Previous research efforts to develop a coronavirus vaccine in the years following the 2003 pandemic have opened the door for the scientist to design a new vaccine for the COVID-19. Both SARS-CoV and SARS-CoV-2 has a high degree of genetic similarity and bind to the same host cell ACE2 receptor. By using different vaccine development platforms including whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines several candidates displayed efficacy in vitro studies but few progressed to clinical trials. This review provides a brief introduction of the general features of SARS-CoV-2 and discusses the current progress of ongoing advances in designing vaccine development efforts to counter COVID-19.

The S protein is a transmembrane glycoprotein that promotes the entrance of the virus into host cells. S protein is a major target for design of vaccines and inhibitors of viral entry. The S protein has two domains, S1 and S2. The S1 domains contain the receptor binding domain (RBD) that mediates attachment to the host receptor cell, whereas the S2 domain facilitates the fusion of the virus to the host cell. The Entry of SARS-CoV-2 into host cells initiated by binding of the RBD to angiotensin-converting enzyme 2 (ACE2), the main receptor for SARS-CoV-2 on the host cells surface and CD209L is another receptor with lower affinity (7) . ACE2 receptors expressed in type II alveolar cells, airway epithelial cells, fibroblasts, endothelial cells, and in several immune cells. S2 subunit has a domain that facilitates the fusion of the viral envelope with the host cell membrane. These domains are internal membrane fusion peptide (FP), a membrane proximal external region (MPER), two 7-peptide repeats, and a transmembrane domain (TM). The S glycoprotein has a key role in the induction of immunity during infection with SARS-CoV-2 by eliciting neutralizingantibodies and T-cell responses. Studies showed that the S protein has several immunodominant parts that do not induce neutralizing antibodies, but the RBD in the S1 region is a potent inducer of neutralizing antibodies. Thus, full-length S glycoprotein, the S1 subunit, the RBD domain, NTD, and FP are proposed as the promising candidate to develop an effective vaccine against SARS-CoV-2 (7), (8) . The M-membrane protein is a transmembrane glycoprotein that gives a definite shape to the virus structure. It binds to nucleocapsid and organizes the virus assembly. The M protein contains T cell epitope clusters that elicit a neutralizing antibody in SARS patients. The E protein has a key role in the pathogenesis, assembly, and release of the virus. The E protein Inactivation modifies the virulence of CoVs due to changes in morphology and tropism. The N-nucelocapsid protein (which is within the phospholipid bilayer) has a key role in complex formation with viral genome, enhances M protein interaction during assembly, and increases replication of the virus. The E, S, and M proteins form the viral envelope (8), (9), (10).

J o u r n a l P r e -p r o o f cases. According to WHO guidelines infected patients treated with supportive care like bed rest, oxygen saturation, adequate nutrition, prevention of dehydration, keeping electrolyte and acid-base balance, antibiotics, and isolation of patients suspected or confirmed for COVID-19 (12) . Several pre-existing and potential drug candidates, including remdesivir, chloroquine, and others are considered. the Therapeutic options that could be evaluated and used for COVID-19 include molecules binding to the virus, inhibiting enzymes involved in viral replication and transcription, inhibitors targeting helicase and proteases, host cell protease inhibitors, host cell endocytosis inhibitors, anti-sense RNA and ribozyme, neutralizing antibodies, mAbs targeting host cell receptor or interfere with S1 RBD, antiviral peptide targeting S2, and natural products (13) .

Effective SARS-CoV-2 vaccines are crucial for controlling the CoVs pandemic. Vaccines decrease disease severity, viral shedding, and person to person transmission. Currently, no vaccine has been licensed to prevent SARS-CoV-2 infection (14) . There are different vaccine development platforms against SARS-CoV-2, including live attenuated virus, viral vectors, inactivated virus, subunit vaccines, recombinant DNA, and protein vaccines. Several studies are in progress, but requires months to years to develop the vaccines for SARS-CoV-2. Currently, there may be many promising targets for SARS-CoV-2. COVID-19 candidate vaccines under development include S protein or RBD subunit vaccines and replicating or non-replicating vector vaccines expressing mainly S protein or the RBD. Several studies showed that viral S protein subunit vaccines displayed higher neutralizing antibody titers and protection than live-attenuated SARS-CoV, full, and DNA-based S protein vaccines. Collectively, S protein/gene is the preferred target site in SARS vaccine development, and the same strategy can be potentially useful in developing SARS-CoV-2 vaccine (14), (15).

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. The LAV contain viable but attenuated live virus with low virulence property that does not cause disease in a person with normal immune systems. They reproduce slowly, and thus remain a continuous source of antigen for a long period after Single immunization, reducing the need for booster dose (16) . Several LAVs are found in the market to protect various disease including mumps, rubella, measles and varicella vaccines. LAV produced by passing virus in cell cultures, in animals or at suboptimal temperatures, allowing less virulent strains selection or by mutagenesis, or deletion of the viral genes that give virulence.

LAV is not suitable for infants, immune-compromised patients, and elderly people due to the risk of 

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. Inactivated whole-virus has several advantages, including low production cost, safe, and does not involve genetic manipulation. IWV is conventional vaccines with mature technology and may become the first SARS-CoV-2 vaccine put into clinical use (19) .

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 (ChiCTR2000032459), Sinovac (NCT04352608) and Wuhan Institute of Biological Products (ChiCTR2000031809) (20).

Subunit vaccines contain pathogen-derived proteins (antigens) with immunogenicity that can elicit the host immune system. Subunit vaccine is safe and easily manufactures by recombinant DNA techniques but requires adjuvant to enhance a immune response. So far, many research institutions initiated the SARS-CoV-2 subunit vaccine, and use the spike glycoprotein S, and its fragments, such as S1, S2, RBD, and nucleocapsid protein as a prime target antigens as shown in table 1 (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) . Since the RBD of S protein directly bind with the ACE2 receptor on host cells, RBD immunization induces specific antibodies that may block this recognition and effectively prevent the invasion of the virus. Most of SARS-CoV-2 subunit vaccines currently under development use RBD as the antigen. In a study in monkeys, recombinant RBD protein was used to successfully reduce viral loads in the lungs and oropharynx and to 

DNA vaccines (DVs) have a plasmid into which a particular gene incorporated that encodes the antigens that identified from the pathogenic microorganism. The bacterial plasmid carrying the desired gene delivered into the host and translated the antigenic protein that stimulates the immune system normally activated by the pathogenic microorganism. DVs elicit both the cell-mediated and humoral immune genome. But, pre-existing immunity against human Ad5 is widespread, hampering its use as a vector for vaccine development (35) . Chimpanzee adenovirus (ChAdOx1) represents an alternative to the human Ad vector due to its safety and lack of preexisting immunity in humans (36) . Mice immunized with the Ad5 vector encoding the S protein-induced systemic neutralizing antibodies and mucosal T-cells immunity. Ad5 vectors encoding the S1 domain of the S protein displayed stronger neutralizing antibody responses than that encoding the full length, suggesting the effect of immune focusing (37) . 

Synthetic Peptide vaccines have chemically produced from fragments of antigens that elicites 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. Fragments of J o u r n a l P r e -p r o o f antigen has B_ and/or Tepitope activity, which affect the specificity of the immune response. Currently, a set of B and T cell epitopes isolated from S and N proteins of SARS-Cov, these epitopes are highly conserved in SARS-CoV-2 and may assist efforts to develop vaccine for covid-19 disease (39) . 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 (40). 

Drug use in pregnancy; a point to ponder!. Indian journal of pharmaceutical sciences

Viral infections. Murray and Nadel's Textbook of Respiratory Medicine

Understanding human coronavirus HCoV-NL63. The open virology journal

Self-medication among pregnant women attending antenatal clinic at Makongoro health centre in Mwanza, Tanzania: a challenge to health systems

Evaluation of Knowledge and Practice of Pharmacy Professionals regarding the Risk of Medication Use during Pregnancy in Dessie Town, Northeast Ethiopia: A Cross-Sectional Study

Over-the-counter medications in pregnancy. American family physician

Safety profile of medication used during pregnancy: results of a multinational European study. pharmacoepidemiology and drug safety

Thalidomide-induced teratogenesis: History and mechanisms

Evaluation of rational drug use at teaching hospitals in

Prescription drug use during pregnancy in Southern Tigray region, North Ethiopia. BMC pregnancy and childbirth

Assessment of drug use among pregnant women in Addis Ababa, Ethiopia. Pharmacoepidemiology and drug safety

Determinants of prescribed drug use among pregnant women in Bahir Dar city administration, Northwest Ethiopia: a cross sectional study. BMC pregnancy and childbirth

Barriers in physical access to maternal health services in rural Ethiopia. BMC health services research

Recent Advances in the Vaccine Development Against Middle East Respiratory Syndrome-Coronavirus

The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines. npj Vaccines

Live attenuated vaccines: historical successes and current challenges

A decade after SARS: strategies for controlling emerging coronaviruses

China coronavirus: Hong Kong researchers have alreadydeveloped vaccine but need time to test it, expert reveals. SouthChina Morning Post

Return of inactivated whole-virus vaccine for superior efficacy. Immunology and cell biology

WHO. DRAFT landscape of COVID-19 candidate vaccines-20

SARS-CoV-2/COVID-19: Viral Genomics, Epidemiology, Vaccines, and Therapeutic Interventions

Artificial molecular clamp: A novel device for synthetic polymerases

Progress and Prospects on Vaccine Development against SARS-CoV-2. Vaccines

Recombinant receptor binding domain protein induces partial protective immunity in rhesus macaques against Middle East respiratory syndrome coronavirus challenge

mRNA vaccines-a new era in vaccinology

COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics

Advances in mRNA vaccines for infectious diseases

Current Insight into the Novel Coronavirus Disease 2019 (COVID-19)

International journal of molecular sciences

Recombinant vaccines and the development of new vaccine strategies. Brazilian journal of medical and biological research

Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pn eumonia after visiting Wuhan

COVID-19 infection: origin, transmission, and characteristics of human coronaviruses

Viral Vectors for Vaccine Development. Novel Gene Therapy Approaches

Viral Vectors. Vaccines for Biodefense and Emerging and Neglected Diseases

Novel viral vectors in infectious diseases

The Design and Development of a Multi-HBV Antigen Encoded in Chimpanzee Adenoviral and Modified Vaccinia Ankara Viral Vectors; A Novel Therapeutic Vaccine Strategy against HBV. Vaccines

Effects of a SARS-associated coronavirus vaccine in monkeys

The COVID-19 vaccine development landscape

Epitope-based chimeric peptide vaccine design against S, M and E proteins of SARS-CoV-2 etiologic agent of global pandemic COVID-19: an in silico approach

COVID-19: Top 60 Drug Treatments in Development: The biopharma industry is ramping up the development of dozens of potential drug therapies and clinical testing in an all-hands effort to combat the pandemic

Virus-like particles as a highly efficient vaccine platform: diversity of targets and production systems and advances in clinical development

Coronavirus COVID-19 impacts to dentistry and potential salivary diagnosis

Virus-like particles in vaccine development. Expert review of vaccines

Development of a COVID-19 vaccine based on the receptor binding domain displayed on virus-like particles. bioRxiv