…the cost of fighting a virus
By Dr Michelina Andreucci
THE World Health Organisation (WHO) established a multinational coalition of vaccine scientists defining a global Target Product Profile (TPP) for COVID-19, identifying favourable attributes of safe and effective vaccines under two broad categories: ‘Vaccines for the long-term protection of people at higher risk of COVID-19, such as healthcare workers, and other vaccines to provide ‘rapid-response immunity for new outbreaks’.
WHO’s coalition has encouraged international co-operation between the organisations developing vaccine candidates, national regulatory and policy agencies, financial contributors, public health associations and governments worldwide for the ensuing manufacturing of a successful vaccine in quantities sufficient to supply all the affected regions of the world, particularly low-resourced countries.
In April 2020, WHO issued a statement representing dozens of vaccine scientists around the world who pledged their collaboration to accelerate the development of a vaccine against COVID-19.
Because COVID-19 is a novel virus target with properties still being discovered and requiring innovative vaccine technologies and development strategies, the risks associated with developing a successful vaccine across all steps of pre-clinical and clinical research are high.
In fact, industry analysis of vaccine development historically shows failure rates of 84-90 percent.
Geopolitical issues, safety concerns for vulnerable populations, and manufacturing challenges for producing billions of doses are compressing schedules to shorten the standard vaccine development timeline, in some cases combining clinical trial steps over months, a process which is typically conducted sequentially over years.
To evaluate the potential for vaccine efficacy, unprecedented computer simulations, and new COVID-19-specific animal models were developed.
However, these methods remain untested by yet unknown characteristics of the COVID-19 virus, and were being organised multi-nationally during 2020.
Of the confirmed active vaccine candidates, about 70 percent are being developed by private companies, with the remaining projects under development by academic, government coalitions and health organisations.
Most of the vaccine developers are small firms or university research teams with little experience in successful vaccine design and limited capacity for advanced clinical trial costs and are manufacturing without partnership by multi-national pharmaceutical companies.
For Zimbabwean scientists, it means they too have a chance to contribute to WHO’s coalition of vaccine scientists’ TPP to develop a vaccine; especially since the Government of Zimbabwe has made available ZW$10 million for this purpose.
An African-centred response is vital for the elimination or control of the epidemic.
The geographic distribution of COVID-19 vaccine development involves organisations in the US and Canada, which together have about 46 percent of the world’s active vaccine research, compared to 36 percent in Asian countries, including China, and 18 percent in Europe.
Scientists of the Coalition for Epidemic Preparedness Innovations (CEPI) reported that early in 2020, 10 different technology platforms to create an effective vaccine against COVID-19 were already under research and development.
The scientists also stated that 115 vaccine candidates were in development as either ‘exploratory’/ ‘pre-clinical’ projects or in ‘Phase One’ safety trials in human participants.
The CEPI classifies the development stages for vaccines as either:
λ ‘exploratory’ – planning and designing a candidate (having no evaluation in vivo),
λ ‘pre-clinical’ – in vivo evaluation with preparation for manufacturing a compound to test in humans, or
λ Initiation of Phase One safety studies in healthy people.
By mid-May 2020, some 159 total vaccine candidates were reported to be in the early stages of development as either confirmed active projects or in ‘exploratory’ or ‘pre-clinical’ development.
Phase One trials test primarily for safety and preliminary dosing in a few dozen healthy subjects.
Following success in Phase One, Phase
Two trials evaluate immunogenicity, dose levels (efficacy based on biomarkers) and adverse effects of the candidate vaccine, typically carried out in hundreds of people.
A Phase One-Two trial conducts preliminary safety and immunogenicity testing, is typically randomised, placebo-controlled, and at multiple sites, while determining more precise, effective doses.
Phase Three trials typically involve more participants, including a control group, and test effectiveness of the vaccine to prevent the disease, while monitoring for adverse effects at the optimal dose.
If accumulating data in trial candidate vaccines provide early insights into positive or negative efficacy of the treatment, a clinical trial design in progress may be modified as an ‘adaptive design’ as results emerge to adjust trial strictures across all study sites within ongoing Phase Two-Three clinical trials on candidate vaccines.
This may shorten trial durations and use fewer subjects (people) and possibly expediting decisions for early termination or success of a vaccine.
If priority criteria are met, candidate vaccines may be added to the solidarity trial as they become available; while vaccine candidates showing poor evidence of safety or efficacy compared to placebo or other vaccines will be dropped from the international trial.
The WHO vaccine coalition will prioritise which vaccines go into Phase Two and Three clinical trials, and determines harmonised Phase Three protocols for all vaccines achieving the pivotal trial stage.
As clinical trials for COVID-19 started in 2020 overseas, African countries were already out of this early matrix.
Vaccine technologies currently being developed for COVID-19 are not, on the whole, similar to vaccines which are already in use to prevent influenza.
Scientists are now using ‘next-generation’ strategies for precision on the COVID-19 infection mechanisms, while hastening its development for the eventual prevention of the infection with a new vaccine.
Vaccine platforms currently in development are also designed to address mechanisms for infection susceptibility to COVID-19 in specific population sub-groups, such as the elderly, children, pregnant women or people with existing weakened immune systems.
China, where the novel coronavirus first broke out in November 2019, pledged US$2 billion to support overall efforts by the WHO for programmes against COVID-19.
Dr Michelina Andreucci is a Zimbabwean-Italian researcher and industrial design consultant. She is a published author in her field.
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