With the SARS-CoV-2 pandemic creating such a wide-reaching health crisis, it is imperative that a safe and effective vaccine be developed promptly for global availability. As such, there are several vaccine development projects currently underway aiming to meet this critical demand. However, COVID vaccine development is not immune to the inherent limitations and challenges that are encountered during vaccine clinical trials.
Unlike the SARS-CoV-1 epidemic in 2003, which largely remained local and quickly vanished from the circulation, SARS-CoV-2 succeeded in rapidly spreading globally1. As a result, we are facing a worldwide COVID pandemic. There is virtually no corner of the world that this highly infectious virus has not touched and there is no certainty regarding when or whether this pandemic will end. With this wide-reaching health crisis, there is an unprecedented need for development of a safe and effective vaccine that can be made globally available2. There are 2 primary goals in a development of a vaccine: (1) protection from infection due to seroconversion and (2) prevention of clinically symptomatic disease (especially amelioration of severe disease that requires high intensity medical care and taxes the medical system)2. If a vaccine succeeds in hitting these 2 aims, then we will see a reduced population transmissibility and prevention of secondary epidemics or pandemics.
Normally, 12–18 months is required to develop a new vaccine (development, clinical trials, and regulatory approval)1. To date, upwards of ninety different vaccines are undergoing development from groups around the world to fight SARS-CoV-2. At least 6 of these groups have started to test the safety and efficacy in human volunteers3. Many vaccine platforms are being utilized in this global effort, which all have unique advantages and limitations (Table 1). Overall, vaccine characteristics that are needed include: speed and flexibility of manufacturing, safety and reactogenicity, production of humoral and cellular immunogenicity, durability of immunity, appropriate scale and cost of manufacturing, vaccine stability and cold chain requirements2. While this swift movement with maximal globally-involved efforts toward vaccine development is encouraging, there are still many challenges to face before a vaccine can be made widely available (Table 2).
Table 1 -
Different vaccine platforms currently being investigated for SARS-CoV-2 and their benefits/limitations2,3
||Teams Currently Working on this Vaccine Platform
||Used in measles and polio vaccines
||Require extensive safety testing
||Passed through animal or human cells to pick up mutations that make it less able to cause disease
||Codagenix (NY)/Serum Institute of India
||Chemicals or heat used to make uninfectious
||Need to start with large quantity of infectious virus
||Sinovac Biotech (Beijing)
|Nucleic-acid vaccines (DNA or RNA)
||Inject genetic instructions coding for mRNA to make coronavirus proteins to prompt an immune response. (most are spike protein)
||Safe and easy to develop Generated quickly Make genetic material only (not virus)
||Unproven, no licensed vaccines use this technology
||At least 20 teams Example: Moderna BioNTech/Pfizer CureVac (mRNA) Inovio (DNA)
||Weakened virus (measles, VZV or AV) engineered to make coronavirus proteins after injected into the body
||Virus that can still replicate within cells
||Safe Provoke strong immune response Potential for large scale manufacturing Example: Ebola vaccine
||Existing immunity to vector virus could blunt vaccine’s effectiveness
||Virus that cannot replicate because key genes have been disabled
||Long history of use in gene therapy
||No licensed vaccines Booster shots needed for long-immunity
||Johnson & Johnson
|Protein-based vaccines (traditional)
||Example: hepatitis B, HPV, VZV, and influenza
||Requires time to establish cell lines for manufacturing
| Protein subunits
||Fragments of coronavirus proteins injected into the body (most focusing on spike protein or its receptor binding domain)
||Similar SARS vaccines protect monkeys against SARS but not tested in people
||Requires adjuvants to stimulate the immune system May need multiple doses of vaccine
||28 teams Example: Sanofi Novavax
| Virus-like particles (VLP)
||Empty virus shells that mimic coronavirus injected into the body
||Not infectious because lack genetic material Can trigger a strong immune response
||Can be difficult to manufacture
Table 2 -
Possible hurtles/limitations to clinical trials creating a vaccine2
|Theoretical risk of vaccination causing subsequent increased infection severity
| Example: Vaccine-associated enhanced respiratory disease
|No in vivo data on type or level of immunity required to protect from subsequent reinfection and duration of that protection
| Trial needs prolonged follow-up of initial vaccine cohort to determine durability of immunity
| Need for testing parameters to distinguish immune response from prior vaccine versus infection
|High mutation rate of single-stranded RNA virus such as SARS-CoV-2 (Genetic drift)
| Though to date, only limited alterations seen in the spike protein
|20%–40% of total COVID-19 cases are asymptomatic
| Would need a greater number of trial enrollees as exact incidence rates are unknown
|Partial efficacy in a young healthy adult does not predict similar effectiveness amount older adults with comorbidities
| Trial inclusion population requires both younger and older populations
Conflict of interest disclosures
The author declares that there is no financial conflict of interest with regard to the content of this report.
1. Wang F, Kream RM, Stefano GB. An evidence based perspective on mRNA-SARS-CoV-2 vaccine development. Med Sci Monit 2020;26:e924700.
2. Corey BL, Mascola JR, Fauci AS, et al. A strategic approach to COVID-19 vaccine R&D. Science 2020;368:948.
3. Callaway E. The race for coronavirus vaccines: a graphical guide. Nature 2020;580:576–7.
Keywords:Copyright © 2020 The Authors. Published by Wolters Kluwer on behalf of the International Federation of Fertility Societies.
SARS-CoV-2 vaccine; COVID vaccine; Coronavirus vaccine