12th August 2020:
As the world struggles with the Covid-19 pandemic, changing the fundamentals of this infection is hugely dependent on vaccines. For example, preventing large numbers of people from being infected and spreading the virus even when they have no signs of disease as well as averting life-threatening illness and the longer-term disabilities. Covid-19 is increasingly turning out to be a multi-system disease. We can be encouraged that there are many different vaccine candidates being developed, a handful of which are now into clinical trials. Ideally, we want a vaccine that interrupts person to person spread of the virus (transmission) as well as preventing disease, but the current trials may not provide clear answers on this. Nonetheless, in the coming weeks and months, we’ll have at least two important kinds of results; data on whether vaccines protect against disease and on the induction of good immune responses (based on blood tests for antibodies and T-cells).
It has been an incredible experience to witness the unprecedented sharing of scientific ideas in the fight against this common enemy. These international collaborations, exchanges of reagents and know-how among scientists have driven innovation at an accelerated pace. But we are fast approaching the time when decisions on the next steps are going to become complicated. If any of the vaccines show clear evidence of protection against Covid-19, then will this guarantee progression to large scale production and implementation and how will these decisions be made?
There are already major partnerships between vaccine research groups and manufacturers. Making enough vaccine to enable clinical trials on a few thousand people is relatively straight forward. Scaling up production for widespread vaccine deployment requires billions of doses – a very different kettle of fish. For example, the UK government has secured early access to manufacturing capacity of 3 different candidate vaccines to the tune of 90 million doses through BioNTech/Pfizer (a mRNA vaccine) and Valneva (an inactivated whole virus vaccine). Astra Zeneca is committed to manufacturing 100 million doses of the Oxford University vaccine (based on the spike protein in an adenovirus vector). In the USA, a deal has been struck between the large pharmaceutical firms Glaxo Smith Kline (GSK) and Sanofi to produce 100 million doses of recombinant protein and mRNA vaccines with later scale up to 1 billion doses in 2021. These are mind-boggling numbers associated with astronomical costs and, of course, pharmaceutical companies are answerable to their shareholders.
European leaders have given assurances that if their laboratories are the first to develop a vaccine, it will be broadly licensed around the world to ensure global access with priority being given to vulnerable populations. In contrast, the USA and China are gripped by an escalating trade war of nationalistic imperatives in which Covid-19 vaccines could become a bargaining chip, a new global arms race to own the patent rights to effective vaccines. There has already been an ominous precedent in the recent controversial machinations over the rights of the drug Remesdevir in the US. Then, yesterday, out of the blue, Vladamir Putin announced that Russia will be implementing a vaccine that has apparently been tested in only hundreds of people with no evidence that it confers protection. Sputnik V seems a brazen example of political expediency2.
So, which vaccines will be chosen to go forward and on what basis? Most trials rely on testing candidate vaccines in young, healthy volunteers, yet the most susceptible people are the elderly, especially those with other health problems such as diabetes, pre-existing lung disease and obesity. We’ll need to know a lot more about the responses of people at different ages. Following natural infection with the Covid19 virus, the duration of protection appears to be short-lived. Vaccines may do better, but even so, repeated immunisations may be needed if immunity wanes. The need for ‘boosting’ raises complex questions as to whether it can be carried out with the original vaccine formulation or whether it will be possible to have a mix and match approach.
Another dominant issue will be concerns about adverse reactions and the safety profiles of different vaccine formulations. Trust in immunisation is critical and recent polls in the UK and USA suggest that hesitancy over Covid-19 vaccines is prevalent. Vaccines are our most powerful public health tool, but people must have confidence in them and the healthcare workers and scientists that administer them. Yet the social factors that underpin personal choices and behaviour concerning immunisation are poorly understood. As Sir Jeremy Farrar cautions in a recent review: “Understanding people and society – through history, sociology, anthropology – is at least as important as understanding viruses and immunology”1.
The problem of evaluating new vaccines and developing policies for their implementation is a well-trodden path. But the urgency and scale of the Covid-19 pandemic challenges their adequacy and appropriateness. For example, governments usually rely strongly on a cost-effectiveness analysis to inform policies on vaccine deployment. This evaluates (using mathematical models) the economic gains of immunisation in relation to the costs of purchasing and distributing a vaccine.
As of August 11th. 2020, more than 20 million people have tested positive for Covid-19 with three quarters of a million deaths; the numbers are still growing at an alarming rate. But there is a jewel that shines undimmed: science can get us through these difficult times. Within weeks of the first case, the Covid-19 virus was identified, its sequence determined and made available to all scientists worldwide. We know how the virus spreads and that no place on earth is exempt. Although the economic and societal penalties are punitive, social distancing, wearing masks and washing hands drastically reduces person to person transmission of the virus. I am optimistic that vaccines and new treatments will become available in the months ahead. Successful science depends on global cooperation. The message could not be clearer.
Copyright Richard Moxon 11.08.20
As mentioned in the Home Page, I will be taking a break for a short while. Thank you all for your incredible interest and input over the past months. Thanks to you, the blog has surpassed my expectations – on one memorable day there were more than 600 hits in a single day. I’ll be back in September, in the meantime I will also be hard at work on the final stages of my book Brain Fever that will be published next year.
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