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Where We are Now in the Race for the COVID-19 Vaccine

By Esco Healthcare 29 September, 2020

Where We are Now in the Race for the COVID-19 Vaccine

The COVID-19 pandemic is an uncharted territory where almost all countries of the world have established the use of mouth-and-nose protection (i.e. face masks, face shield) to prevent virus transmission. As part of the comprehensive package of heath measures, everyone is advised to wash their hands, to practice social distancing, and to sanitize. The spreading rate is so high that entertainment establishments, recreational areas, and even some nations are on lockdowns which triggered global economic downturns.

The Question of What.

Vaccines are hailed to be an exit strategy for this surging pandemic. They do not just help keep a person healthy but also greatly affect the community conclusively. If a significant number of the population is vaccinated, the spread of disease can be stopped. A recently released vaccine landscape from WHO shows what vaccines are underway to completion.

Frontrunners for producing a candidate vaccine are in Phase 3, each having different strategies on how to activate an immune response.

COVID_19_candidate_vaccines_table
Table 1

COVID-19 candidate vaccines based on the tabulated data from WHO

Vaccine Vaccine Platform No. of doses Timing of doses
3 LNP-mRNAs
BioNTech/Fosun Pharma/Pfizer
RNA 2 0, 28 days
Ad26COVS1
Janssen Pharmaceutical Companies
Non-replicating
Viral Vector
2 0, 56 days
Adeno-based (rAd26-S+rAd5-S)
Gamaleya Research Institute
Non-replicating
Viral Vector
2 0, 21 days
Adenovirus Type 5 Vector
CanSino Biological Inc./Beijing Institute of Biotechnology
Non-replicating
Viral Vector
1
Adjuvanted recombinant protein (RBD-Dimer)
Anhui Zhifei Longcom Biopharmaceutical/Institute of Microbiology, Chinese Academy of Services
Protein Subunit 2 or 3 0, 28 or 0, 28, 56 days
ChAdOx1-S
University of Oxford/AstraZeneca
Non-replicating
Viral Vector
1
DNA plasmid vaccine + Adjuvant
Osaka University/AnGes/Takara Bio
DNA 2 0, 14 days
DNA plasmid vaccine
Cadila Healthcare Limited
DNA 3 0, 28, 56 days
DNA plasmid with electroporation
Inovio Pharmaceuticals/International Vaccine Institute
DNA 2 0, 28 days
Full length recombinant SARS-CoV-2 glycoprotein nanoparticle vaccine adjuvanted with Matrix M
Novavax
Protein Subunit 2 0, 21 days
GX-19 DNA vaccine
Genexine Consortium
DNA 2 0, 28 days
Inactivated
Sinovac
Inactivated 2 0, 14 days
Inactivated
Beijing Institute of Biological Products/Sinopharm
Inactivated 2 0, 14 or 0, 21 days
Inactivated
Institute of Medical Biology, Chinese Academy of Medical Sciences
Inactivated 2 0, 28 days
Inactivated
Research Institute for Biological Safety Problems, Rep of Kazakhstan
Inactivated 2 0, 21 days
Inactivated
Wuhan Institute of Biological Product/Sinopharm
Inactivated 2 0, 14 or 0, 21 days
Intranasal flu-based-RBD
Beijing Wantai Biological Pharmacy/Xiamen University
Replicating Viral
Vector
1
LNP-encapsulated mRNA
Moderna/NIAID
RNA 2 0, 28 days
LNP-nCoVsaRNA
Imperial College London
RNA 2
Measles-vector based
Institute Pasteur/Themis/Univ. of Pittsburg CVR/ Merck Sharp & Dohme
Replicating Viral
Vector
1 or 2 0, 28 days
Molecular clamp stabilized spike protein with MF59 adjuvant
University of Queensland/CSL/Seqirus
Protein Subunit 2 0, 28 days
mRNA
Arcturus/Duke-NUS
RNA
mRNA
CureVac
RNA 2 0, 28 days
mRNA
People’s Liberation Army (PLA Academy of Military Sciences/Walvax Biotech
RNA 2 0, 14 or 0, 28 days
Native like Trimeric subunit spike protein vaccine
Clover Biopharmarceuticals Inc./GSK/Dynavax
Protein Subunit 2 0, 21 days
Peptide
FBRI SRC VB VECTOR, Rospotrebnadzor, Koltsovo
Protein Subunit 2 0, 21 days
Plant-derived VLP adjuvanted with GSK or Dynavax adjs.
Medicago Inc.
VLP 2 0, 21 days
RBD (baculovirus production expressed in Sf9 cells)
West China Hospital, Sichuan University
Protein Subunit 2 0, 28 days
RBD+Adjuvant
Instituto Finaly de Vacunas, Cuba
Protein Subunit 2 0, 28 days
RBD-based
Kentucky Bioprocessing, Inc.
Protein Subunit 2 0, 21 days
Recombinant spike protein with Advax™ Adjuvant
Recombinant spike protein with Advax™ Adjuvant
Protein Subunit 1
Replication defective Simian Adenovirus (GRAd) encoding S
Reithera/LEUKOCARE/Univercells
Non-replicating
Viral Vector
1
S protein (baculovirus production)
Sanofi Pasteur/GSK
Protein Subunit 2 0, 21 days
S-2p protein + CpG 1018
Medigen Vaccine Biologics Corporation/ NIAID/Dynavax
Protein Subunit 2 0, 28 days
Whole-Virion Inactivated
Bharat Biotech
Inactivated 2 0, 14 days

Note: The table above represents the current frontrunners for COVID-19 candidate vaccines based on the tabulated data from WHO. Further information regarding the whole pipeline can be found here.

With COVID-19 information early release to the public, scientists pushed forward to study the model of the virus. Each of the COVID-19 vaccine mentioned have identified and used the SARS-CoV-2 spike glycoprotein, which the virus uses to infect cells, to trigger the immune system. This in turn will generate protective antibodies and a dedicated immune response to the virus once introduced to the system. The protective antibodies will act through preventing the spike glycoprotein from attaching the virus to human cells, thereby neutralizing the SARS-CoV-2 virus that causes COVID-19.

The Question of When and Why.

Whether the world is ready to produce billions of vaccines to accommodate the population, let us look on how vaccines are produced (Fig.1)

Vaccine productive timeline
Figure 1

A general overview of the vaccine production timeline.

Vaccine productive timeline

Vaccines take time before they are released in the market. Some have high hopes that a usable vaccine will be released by the end of this year or next year. The coronavirus vaccine landscape has about at least 180 potential candidates in the pipeline (35 candidates for clinical evaluation; 145 candidates for preclinical evaluation).

The pre-clinical stage takes 1-2 years, from the start of discovery to exploration of the targeted antigen. It requires extensive effort to make sure each step is done safely and precisely. However, if a certain vaccine is approved, testing, mass-manufacturing, and distributing these vaccines fairly and affordably will be another challenge. This landscape is divided into three types of vaccines: RNA (Fig.2), attenuated (Fig.3), and inactivated (Fig. 4).

RNA vaccine workflow
Figure 2

RNA vaccine workflow

RNA vaccine workflow

RNA vaccines are faster and cheaper to make. One of its major advantages is that RNA can be produced from a DNA template in the laboratory using readily available materials. Its mechanism comprises of mRNA strand that codes for a disease-specific antigen. Once introduced into the body, the cells use the genetic information from the mRNA strand to produce the antigen; therefore, activating an immune response.

As RNA vaccines are not made with pathogenic particles or inactivated pathogen, they are deemed safe to use. In terms of production, they can be produced rapidly with faster scalability, improving emerging outbreak response.

Attenuated vaccine workflow
Figure 3

Attenuated vaccine workflow

Attenuated vaccine workflow

Live, attenuated vaccines are known to be the best teachers for the immune system. The reason behind is: attenuated form of the virus is nearly identical to a natural infection. Mostly with a single dose, the recipient produces immunity against the disease. While this is true, attenuated vaccines takes longer time to make due to the manufacturing capabilities, as well as parameter optimization to obtain maximum results. One must keep an eye on how these manufactured vaccines are stored to maintain its best condition, its limitation of use, and possible reversion to virulence.

Inactivated vaccines are vaccines where the produced bacterium or virus in culture media is “killed” or inactivated with heat or chemicals such as formalin. In other cases, the antigen is purified and treated to obtain components that are to be included in the vaccine (e.g. polysaccharide).

Inactivated vaccine workflow
Figure 4

Inactivated vaccine workflow

Inactivated vaccine workflow

In general, inactivated vaccines do not produce protective immunity on the first dose. It primes the immune system and will develop a protective response on the second or third dose. The response is mostly humoral as compared to attenuated vaccines: antibody titers against inactivated antigens diminish with time. In terms of production, this type of vaccine is costlier due to the duration of immunity; thus, requiring booster shots, requirement for adjuvant, and more.

Where we stand now in the course of the pandemic is changing. Although it takes 12-36 months to manufacture a vaccine alone, its promise to protect the people remains the same.

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References:
  1. Bill & Melinda Gates Foundation. Production Economics for Vaccines. 2016. https://docs.gatesfoundation.org/Documents/Production_Economics_Vaccines_2016.pdf> [accessed 15.09.20]
  2. CDC. (2018). Understanding how vaccines work. Retrieved from https://www.cdc.gov/vaccines/hcp/conversations/downloads/vacsafe-understand-color-office.pdf. Accessed by 09 Sept. 2020.
  3. D’Amore, T. and Yang, Y. (2019). Advances and challenges in vaccine development and manufacturing. https://bioprocessintl.com/manufacturing/vaccines/advances-and-challenges-in-vaccine-development-and-manufacture/> [accessed 15.09.20]
  4. Gomez, P. and Robinson, J. (2018). Vaccine manufacturing. Plotkin’s vaccines. 2018: 51-60 e.1. doi: 10.1016/B978-0-323-35761-6.00005-5
  5. Plotkin et. al. (2017). The complexity and cost of vaccine manufacturing – An overview. Vaccine; 35(33): 4064-4071. doi: 10.1016/j.vaccine.2017.06.003. PMCID: PMC5518734
  6. World Health Organization (2020). Draft landscape of COVID-19 candidate vaccines. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines> [accessed 10.09.20]
  7. World Health Organization. Immunization Standards. Vaccine quality. http://www.who.int/immunization_standards/vaccine_quality/en/> [accessed 10.09.20]