Vaccine and Drug Development for COVID-19

April 16, 2020 Rima Medical Science 0

There is an expectation among people that the development of treatment of COVID-19 should proceed and succeed as quickly as possible. However, vaccine development process is a lengthy process which may take an average of two to five years (considering minimum time) or more than that.

Vaccine

  • A vaccine is “an inactivated or attenuated pathogen or a component of a pathogen (nucleic acid, protein) that when administered to the host, stimulates a protective response of the cells in the immune system,” or it is “an immune-biological substance designed to produce specific protection against a given disease.”
  • Vaccines are considered one of the most impressive success stories of medicine. The success of currently available vaccines is based on their ability to induce antibodies that block or neutralize infectious agents or their products.
  • The successful eradication of smallpox (worldwide cases reduced from 2 million per year in 1959 to zero in 1978), and estimated avoidance of 2.5 million deaths per year from diphtheria, tetanus, whooping cough and measles through immunization (WHO/UNICEF, 2010), exemplify their power and significance for global health.

Immunological challenges for vaccine development

  • The development of new and effective vaccine depends on detailed understanding of the immune corelates of the protection.
  • To develop vaccine against virus, the first step should be studying about most up-to-date version of the virus. Scientists should be able to grow the virus, which may thrive in host organisms but is fragile outside of them, in cell culture. If they can develop a helpful animal model, it can be used to study the viral mechanism; how it enters inside body, which part it goes to, which cells or tissues it invades and how it causes organ failure or death.
  • All these steps are time consuming and labor-intensive.

Rigors needed in vaccine clinical trials

  • Once the vaccine is developed, its safety and efficacy are tested in suitable candidates in succeeding stages of clinical trials.
  • In preclinical phase, its safety is tested in animals like rats, mice, guinea pig.
  • In ‘Phase I’ of clinical trials, human studies of acceptable safety and reactogenicity of vaccine are studied. Candidates are healthy human beings. In this phase, safety and tolerability are evaluated at both the local and systemic levels. Dose-ranging and/or repeated-dose studies are often performed. Preliminary information on immunogenicity and efficacy may be collected. These trials are often designed as randomized, double-blind, placebo-controlled, single-center studies.
  • In ‘Phase II’, the ‘proof-of-concept’ (PoC) of the vaccine product should be ensured. Candidates are large number of target population. In this, immunogenicity of the relevant active component(s) and the safety profile of a vaccine within the target population are studied. Clinically applicable vaccine regimen like dose and number of doses, sequence/interval between doses, and route of administration are determined.
  • ‘Phase III’ trial is intended to provide a pivotal conclusion needed for marketing approval. The safety and efficacy of vaccine should be accessed in large scale target population. The designs of Phase II and Phase III clinical trials are similar, but the size of a Phase III trial is much larger.
  • The information obtained are summarized and filed for submission to regulatory authorities in support of an application for marketing approval. The WHO and each regulatory authority have their own guidelines to ensure the quality of the information provided. The multidisciplinary FDA review team reviews the efficacy and safety information needed to make a risk-benefit assessment, appropriateness of label contents and the reliability of the manufacturing process and is advise by Vaccines and Related Biological Products Advisory Committee (VRBPAC).
  • After obtaining government approval and market launch, many vaccines undergo post licensure- ‘Phase IV’ studies. It’s because even though a vaccine may be licensed, the safety information provided for approval is regarded as insufficient, because at that point, only a few thousand people have likely been exposed to the vaccine.
  • Each phase of clinical trials a long time to design and setup; how many patients to recruit, which hospital and institutions to collaborate with. Massive amount of data is collected during different phases, so documentation requires tremendous amount of human resources and time. After marketing approval, vaccine need to be produced in large amount and supply chain need to be set up before distribution.
  • Overall, the entire process takes several years.

The development of a COVID-19 vaccine

  • In case of SARS-CoV-2-virus, the process can be expedited as the genetic sequence of SARS-CoV-2-virus is already published on 11 January 2020 and multiple institutions are working together to develop the vaccine.
  • The most advanced vaccine candidates for COVID-19 which have recently moved into clinical development are mRNA-1273 from Moderna, Ad5-nCoV from CanSino Biologicals, INO-4800 from Inovio, LV-SMENP-DC and pathogen-specific aAPC from Shenzhen Geno-Immune Medical Institute.
  • Numerous novel approaches are being accessed worldwide for developing vaccine against COVID-19. For instance, Ji et al are accessing a novel approach to develop viral antigen displaying decoy cells as vaccine to protect against COVID-19 disease. Their approach is to modify cells to express viral markers to elicit protective immunity responses (decoy cellular vaccination).
  • The global vaccine R&D effort in response to the COVID-19 pandemic is unprecedented in terms of scale and speed. there is an indication that vaccine could be available under emergency use or similar protocols by early 2021. This would represent a fundamental step change from the traditional vaccine development pathway, which takes on average over 10 years, even compared with the accelerated 5-year timescale for development of the first Ebola vaccine, and will necessitate novel vaccine development paradigms involving parallel and adaptive development phases, innovative regulatory processes and scaling manufacturing capacity.

References

  1. Stefan HE Kaufmann, MJuliana McElrath, David JMLewis, GiuseppeDel Giudice. Challenges and responses in human vaccine development. Current Opinion in Immunology. June 2014;28: 18-26.
  2. Seunghoon Han. Clinical vaccine development. Clin Exp Vaccine Res. 2015 Jan; 4(1): 46–53.
  3. Chandrakant Lahariya. Vaccine epidemiology: A review. J Family Med Prim Care. 2016 Jan-Mar; 5(1): 7–15.
  4. Petra Oyston, Karen Robinson. The current challenges for vaccine development. Journal of Medical Microbiology. 2012. 61(7): 889-894.
  5. Tung Thanh Le, Zacharias Andreadakis, Arun Kumar, Raúl Gómez Román, Stig Tollefsen, Melanie Saville, Stephen Mayhew. The COVID-19 vaccine development landscape. Nature reviews drug discovery. 9 April 2020.
  6. Ji H, Yan Y, Ding B, Guo W, Brunswick M, Niethammer A, SooHoo W, Smith R, Nahama A, Zhang Y. Novel decoy cellular vaccine strategy utilizing transgenic antigen-expressing cells as immune presenter and adjuvant in vaccine prototype against SARS-CoV-2 virus. Med Drug Discov. 2020 Mar; 5: 100026.