A vaccination program to meet the needs of a global pandemic

In the current pandemic, healthcare systems around the world are struggling to cope with the burden of hospital and critical care admissions resulting from COVID-19. Therefore, the ability of a vaccine to protect against severe disease and death is of critical importance.

A vaccine against COVID-19 which is capable of reducing disease severity could have a huge impact on the course of the pandemic.1 It is possible that these vaccines may be able to prevent infection and even transmission, which will better help to control disease and pave the way for an easing of the kinds of non-pharmaceutical restrictions currently in place in many countries and regions, such as social distancing and the wearing of masks.


Figure 1 – Potential endpoints of an efficacious COVID-19 vaccine. Adapted from Hodgson SH et al. Lancet Infect Dis 2020.1


The World Health Organisation (WHO) has defined the minimum efficacy threshold for acceptance of any COVID-19 vaccine as 50%, which could be determined against disease, severe disease and/or transmission of the virus.2 Published modelling data have demonstrated that vaccine efficacy at 60% could have a significant impact on the course of the pandemic, reducing disease severity and hospitalisation rates; 80% efficacy may be able to bring an end to the pandemic, meaning measures such as social distancing could be completely relaxed.3,4 These data consider uptake within a community and offer a target at which to aim when developing COVID-19 vaccines.

Developing an effective vaccine

Beyond efficacy, an effective vaccine should demonstrate immunogenicity, durability of protection, safety, ease of use and uptake within a healthcare setting.



Correlation between immune response and durability

The level of immune response needed from any vaccine to prevent COVID-19 has not yet been determined. Typically, the immune response induced by a vaccine would be compared to the immune response found in people who have known immunity to a disease.5 High levels of neutralising antibodies have been demonstrated in individuals who have recovered from SARS-CoV-2 infection. In addition, emerging data suggest that a T-cell response could play an important role in mitigation of the disease. Some individuals who have been infected with the virus but remained asymptomatic, have developed a robust T-cell response with an absence of detectable antibodies. Rapid induction of T-cells against the SARS-CoV-2 virus may be important in prolonging protection against COVID-19.6

Immunogenicity assesses the type of immune response that a vaccine generates and its magnitude over time, and thus it can be a surrogate measure of protection. While it is too soon to gauge the duration of effect of a COVID-19 vaccine, we can refer to results from a previous clinical trial of a vaccine in development against another coronavirus (responsible for causing Middle East Respiratory Syndrome [MERS]) in which an adenoviral vector platform was used. These results demonstrated that the vaccine-induced immune response was maintained for over a year.7

Safety

Safety is paramount in any drug development programme. For vaccines in particular, the standard of testing and monitoring is higher than for most other medicines, as vaccines are administered to healthy people.8

This is not the first time in history that a vaccine is being developed at a faster pace than usual in order to meet public health demands. Following the Ebola outbreak in Guinea in 2016, a vaccine went from early testing to clinical trials within approximately 10 months, which was unprecedented at that time. When a new outbreak of Ebola emerged in 2018, an adenoviral vector vaccine was administered to approximately 300,000 people, which helped to slow the spread of the disease and save lives.9



Over the past 15 years, pandemic preparedness programmes have identified platforms and technology to allow a rapid response to viral pandemics.10 The wealth of documented experience with several types of vaccines in humans is reassuring. This includes experience with approved vaccines across different platforms, such as the one against hepatitis B – a recombinant viral protein that has been available since 1986.11 Recent clinical trial research using viral‑vectored vaccines in Ebola12 prostate cancer,13 MERS,4 malaria, tuberculosis, and influenza14 have also consistently demonstrated acceptable safety profiles. This pre-existing work has been leveraged in the development of COVID-19 vaccines and will encourage public confidence in this approach.


Performing studies in different geographical locations will support an understanding of safety, but also efficacy, in different demographics and sub-populations. It will also help to ensure that the data available have global relevance and instil public confidence in any vaccination programme. The science will not stop should a vaccine be approved, and post-marketing clinical trials will continue to inform longer-term use and address access for specific sub-populations, such as pregnant women and children.

Regulatory frameworks to support an agile approach15,16

Regulatory agencies across the world are working to ensure vaccine data submitted for approval meet the stringent efficacy and safety standards. Regulators will only reach a decision when they are satisfied there are sufficient efficacy, safety and quality data available.

Under the special circumstances of a pandemic, regulatory authorities have accelerated approval systems in place. For example, the US Food and Drug Administration can grant an Emergency Use Authorisation,17 and the European Medicines Agency can provide support for early access through accelerated assessments.18 For lower-income countries that may lack robust regulatory processes, the WHO provides Emergency Use Listings to expedite the availability of vaccines during public health emergencies.19

Regulators from many countries across the world have implemented rolling reviews to enable flexibility in the assessment of data as they become available during the COVID-19 pandemic. These rolling reviews will continue until sufficient data are available to support submission of a formal application for approval.20

Ensuring a broad, equitable supply: The cornerstone of any successful global vaccination programme

WHO collaborators have demonstrated that the global public health value of a vaccine is only maximised by ensuring equitable access.21 To change the course of the pandemic quickly, a COVID-19 vaccine needs to be available globally and be accessible to all who need it. The COVAX platform has engaged in discussions with 172 countries and is working with governments and manufacturers to ensure that COVID-19 vaccines are available worldwide to both higher- and lower-income countries.22 To achieve this, the scalability of production and manufacturing capacity are essential.

In addition, to ensure the maximum speed of delivery of a vaccine, logistical aspects are crucial. Stability, ease of use (i.e. no need for specially-trained medical staff) and simplicity of distribution, ideally by using a cold chain that is already in place for other vaccines, should be considered.3 Manufacturing capacity needs to scale as quickly as possible to enable rapid access to as many countries as possible following approval by the regulators. Furthermore, setting up local and regional supply chains will reduce the need for transport and any export or import constraints to produce billions of doses around the world at pace.

It is clear that to overcome the COVID-19 pandemic, more than one vaccine will be needed. People need vaccines to do different things – to work better in older people or in children, or to alleviate disease severity. Providing broad equitable access of the COVID-19 vaccines to those in need will enable us to truly alter the course of this pandemic and positively impact the real-word effectiveness of this unprecedented vaccination programme.


References

1. Hodgson SH, et al. What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2 Lancet Infect Dis 2020 [Epub ahead of print]. Available at: https://dx.doi.org/10.1016/S1473-3099(20)30773-8 (Accessed 18 November 2020)

2. World Health Organisation. WHO target product profiles for COVID-19 vaccines. Available at: https://www.who.int/publications/m/item/who-target-product-profiles-for-covid-19-vaccines (Accessed 18 November 2020)

3. The Lancet COVID-19 Commissioners, Task Force Chairs, and Commission Secretariat. Lancet COVID-19 Commission Statement on the occasion of the 75th session of the UN General Assembly. Lancet 2020;396:1102–1124

4. Bartsch SM, et al. Vaccine efficacy needed for a COVID-19 coronavirus vaccine to prevent or stop an epidemic as the sole intervention. Am J Prev Med 2020;59:493–503

5. World Health Organisation. Guidelines on clinical evaluation of vaccines: regulatory expectations. Available at: https://www.who.int/biologicals/BS2287_Clinical_guidelines_final_LINE_NOs_20_July_2016.pdf (Accessed 18 November 2020)

6. Sekine, T, et al., Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. BioRxiv. 2020. Available at: https://dx.doi.org/10.1101/2020.06.29.174888 (Accessed 18 November 2020)

7. Folegatti PM, et al. Safety and immunogenicity of a candidate Middle East respiratory syndrome coronavirus viral-vectored vaccine: a dose-escalation, open-label, non-randomised, uncontrolled, phase 1 trial. Lancet Infect Dis 2020;20:816–826

8. Vaccine Knowledge Project. How vaccines are tested, licensed and monitored. Available at: https://vk.ovg.ox.ac.uk/vk/vaccine-development (Accessed 18 November 2020)

9. World Health Organisation. The vaccines success story gives us hope for the future. Available at: https://www.who.int/news-room/feature-stories/detail/the-vaccines-success-story-gives-us-hope-for-the-future (Accessed 18 November 2020)

10. Sempowski GD, et al. Pandemic preparedness: Developing vaccines and therapeutic antibodies for COVID-19. Cell 2020;181:1458–1463

11. US Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine – Preventable diseases. Available at: https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/hepb.pdf (Accessed 18 November 2020)

12. Monath, T, et al., rVSVΔG-ZEBOV-GP (also designated V920) recombinant vesicular stomatitis virus pseudotyped with Ebola Zaire Glycoprotein: Standardized template with key considerations for a risk/benefit assessment. Vaccine X. 2019 Apr 11; 1: 100009.

13. Capuccini F, et al. Safety and immunogenicity of novel 5T4 viral vectored vaccination regimens in early stage prostate cancer: a phase 1 clinical trial. J Immunother Cancer 2020;8:e000928

14. Ewer KJ, et al. Viral vectors as vaccine platforms: from immunogenicity to impact. Curr Opin Immunol 2016;41:47–54

15. US Food and Drug Administration. Coronavirus Treatment Acceleration Program (CTAP). Available at: https://www.fda.gov/drugs/coronavirus-covid-19-drugs/coronavirus-treatment-acceleration-program-ctap (Accessed November 18, 2020)

16. European Medicines Agency. EMA’s governance during COVID-19 pandemic. Available at: https://www.ema.europa.eu/en/human-regulatory/overview/public-health-threats/coronavirus-disease-covid-19/emas-governance-during-covid-19-pandemic (Accessed 18 November 2020)

17. US Food and Drug Administration. Emergency Use Authorization. Available at: https://www.fda.gov/emergency-preparedness-and-response/mcm-legal-regulatory-and-policy-framework/emergency-use-authorization (Accessed 18 November 2020)

18. European Medicines Agency. Support for early access. Available at: https://www.ema.europa.eu/en/human-regulatory/overview/support-early-access (Accessed 18 November 2020)

19. World Health Organisation. Emergency use listing of vaccines. Available at: https://www.who.int/medicines/regulation/prequalification/prequal-vaccines/EUL_PQ_Vaccines/en/ (Accessed 18 November 2020)

20. European Medicines Agency. EMA starts first rolling review of COVID-19 vaccine in the EU. Available at: https://www.ema.europa.eu/en/news/ema-starts-first-rolling-review-covid-19-vaccine-eu (Accessed 18 November 2020)

21. Hogan AB, et al. Report 33: Modelling the allocation and impact of a COVID-19 vaccine. Imperial College London. Available at: https://www.imperial.ac.uk/media/imperial-college/medicine/mrc-gida/2020-09-25-COVID19-Report-33.pdf (Accessed 18 November 2020)

22. World Health Organisation. 172 countries and multiple candidate vaccines engaged in COVID-19 vaccine Global Access Facility. Available at: https://www.who.int/news/item/24-08-2020-172-countries-and-multiple-candidate-vaccines-engaged-in-covid-19-vaccine-global-access-facility#:~:text=172%20economies%20are%20now%20engaged,they%20are%20licensed%20and%20approved (Accessed 18 November 2020)


Veeva ID: Z4-29097
Date of Preparation: November 2020


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