SCIENTISTS are working around the clock to develop and test vaccines against SARS-CoV-2, the causative agent of COVID-19. Experts agree that widespread use of safe and effective vaccines will rapidly contain the COVID-19 pandemic, preventing transmission and disease.
A key step in the process of any vaccine development is clinical testing, which involves assigning a vaccine or a placebo to human subjects, then evaluating the health effects over a period of time. This testing helps to demonstrate safety in diverse human populations living in different settings, and to determine vaccine efficacy – the ability to prevent infection and disease.
Globally, COVID-19 vaccine trials are being conducted in all continents, representing all diverse human populations in the world. In Africa, Egypt and South Africa are participating in these trials. Many other countries are also preparing to participate.
To date, there are 260 COVID-19 vaccine candidates at different stages of development. Sixty of these are undergoing clinical testing (human trials) in different phases. This includes phase III trials – the point at which scientists aim to determine how well a vaccine protects (efficacy) trial participants from infection or severe COVID-19 symptoms.
November 2020 has been a celebratory month. Preliminary phase III data of three different COVID-19 vaccine candidates showed impressively high efficacy ranging from 70% to 95%. All three – Pfizer/BioNTech, Moderna mRNA-1273 and Oxford ChAdOx1-S vaccines – are in the late stage of phase III clinical trials. Pfizer/BioNTech and Oxford ChAdOx1-S are being tested in Africa too. After investigations of an initial safety concern in phase III trial, the Oxford ChAdOx1-S vaccine testing has proceeded well.
The groundbreaking developments offer hope and optimism. But there are still major obstacles ahead, particularly for developing countries. Chief among these is the fact that at least one of the vaccines showing promise needs to be kept at extremely low temperatures prior to use. This will be a difficult task for most African countries.
In addition, there are concerns about access to the vaccines once manufacturing starts. Among the key concerns is the availability of sufficient vaccine doses to meet the high demand. And then there’s the question of affordability. Resources will be urgently needed to procure and distribute COVID-19 vaccines at a rapid pace.
A great deal of focus is being placed on the COVAX Facility, a GAVI co-led global risk sharing plan. This is overseeing the pooling of procurement and equitable distribution of eventual COVID-19 vaccines.
There are three vaccines at phase III stage with a similar choice of an antigen – the SARS-CoV-2 spike protein. But they work differently in the way they teach the immune system to protect our bodies from COVID-19.
Pfizer/BioNTech is a mRNA vaccine. Such vaccines work by instructing the human cells to make a small part of the virus surface protein and induce the appropriate type of immune response that is thought to confer protection. In this case, it is an immune response to the SARS-CoV-2 spike protein. This protein plays a key role in enabling coronaviruses to infect human cells and replicate.
In some infected people, COVID-19 disease develops, whereas others remain asymptomatic, without any signs or symptoms of the disease. Preliminary data show no major safety concerns are associated with a two-dose administration of the vaccine. This mRNA-based COVID-19 vaccine induces T-cell and strong neutralising antibody immune responses. Both T-cell and antibody immune responses are thought to be critical in protecting against COVID-19. A similar mRNA vaccine, made by Moderna, has shown comparable results.
Efficacy of 95% has been reported for the Pfizer/BioNTech (mRNA) vaccine, far exceeding the expectations. This type of vaccine can be rapidly manufactured and scaled to capacity to meet the high demand for millions of doses. If licensed, it will be the first mRNA vaccine approved for human use by the regulatory authorities.
Oxford ChAdOx1-S is a non-replicating viral vector vaccine. The viral vector, or backbone, used in this vaccine is based on the chimpanzee adenovirus (ChAd). The choice of this type of vector is to circumvent common pre-existing immunity to human adenoviruses (HAdV) that would blunt the ability of such a vaccine to engage the human immune system.
Already, scientists have experience with clinical testing (safety and immunological profiles) of the ChAd viral vectored vaccines.
The Oxford ChAdOx1-S works by using a replication-deficient adenovirus vector to conveniently deliver the spike protein to immune cells or tissues, thereby inducing the desired immune response against SARS-CoV-2. The vaccine-induced immunity comprises of T-cell and strong neutralising (infection-blocking) antibody immune responses.
Novavax NVX-CoV2373 is a protein subunit vaccine. Subunit vaccines work by presenting a specific antigen that stimulates the immune system to mount a response. Importantly, these types of vaccines require combination with adjuvants (a compound that enhances an immune response), as the antigens alone are not enough to induce optimal and long-term immunity.
The antigen (spike protein) in NVX-CoV2373 vaccine is made and purified from cell culture, then formulated – along with Novavax’s saponin-based Matrix-M adjuvant – to a nanoparticle. There is vast clinical experience of this type of vaccine platform in terms of safety and immunogenicity, such as the seasonal influenza vaccine.
Preliminary data show NVX-CoV2373 vaccine-induced immunity comprises T-cell and strong neutralising antibody immune responses. It is likely this two-dose schedule vaccine candidate will show high efficacy.
A big challenge for the Pfizer/BioNTec vaccine is the cold chain requirements. It needs to be transported and stored at unusually low temperatures (-70°C, on dry ice) prior to use. Immunisation programmes – particularly those on the continent – don’t have the vaccine supply and cold chain infrastructures that can optimally handle this vaccine. This is especially true at the level-one healthcare facilities where immunisations routinely take place.
This means that significant investments will have to be made prior to rollout to communities in remote areas. This could cause massive delays in the use of the vaccine, especially in low- and middle-income countries. The good news is that innovative approaches, such as design and development of appropriate transport containers, may address these challenges.
The other two vaccines can be handled within the current immunisation cold chain infrastructure that keeps temperature at a range of 2°C to 8°C prior to use.
Another potential challenge is that the use of any of these vaccines by national immunisation programmes will need to be informed by high quality and timely evidence that takes local context into consideration. This means national policy makers must urgently and meticulously consider the merits and demerits of each of the vaccines prior to deciding which one to use.
On cost and access, a great deal of effort is being put into the COVAX Facility. This seems to be Africa’s only insurance policy against being the last in the queue.