What to expect from the next generation of Covid-19 vaccines

Organisations behind the most advanced coronavirus vaccines, unknown to many a year ago, have fast become familiar: BioNTech, the Gamaleya Institute and Sinopharm, to name but three. Aside from these, universities, biotechnology firms and well-known pharmaceutical companies are working on yet-to-be-released vaccines that could be approved over the coming year. Many of the 200-plus coronavirus vaccines listed by the World Health Organisation as under development are based on alternative technology to those now being rolled out, raising the prospect of a very different vaccine landscape emerging in 2021. A diversity of vaccines is seen as beneficial because, among other things, it means the manufacturing and distribution capabilities of multiple companies can be engaged. The Pfizer-BioNTech and Moderna vaccines, both based on messenger RNA (mRNA) and approved for use, are as much as 95 per cent effective, so there may be limited opportunity for later vaccines to achieve better clinical performance. There are, however, other benefits they could offer. “The principal improvement would be cost,” said Prof Ian Jones, a virologist at the University of Reading in the UK. “The best current vaccines, the RNA vaccines, already provide effectively 100 per cent immunity, so there is no further improvement possible. “However, they are expensive so to provide the same level of protection at a cheaper unit cost would be an advantage.” Reports indicate Moderna charges about $35 (Dh128.6) per dose, while the Pfizer-BioNTech vaccine costs around $20 (Dh73.5) per dose, although prices paid by different authorities vary. Much cheaper is the Oxford-AstraZeneca vaccine, said to cost just $3 to $4 per dose, but in clinical trials it was less effective than other vaccines that have released data so far, preventing 70.4 per cent of Covid-19 cases on average, although this reaches 90 per cent if a half-dose is given initially. Altering the length of time between the two doses, or combining the vaccine with the Sputnik V jab from Russia, may offer further improvements. These jabs are both known as adenoviral vector vaccines because they employ types of viruses called adenoviruses with coronavirus genetic material added. Once injected into patients, the coronavirus genes cause human cells to produce coronavirus spike proteins, and the immune system’s reaction against these offers protection against the pathogen. Easier distribution Aside from looking to improve clinical performance, researchers want to make vaccine distribution easier. The Pfizer-BioNTech vaccine must be stored at -70 to -80°C, so the companies are developing a version, possibly in powdered form and likely to be released in 2021, that does not deteriorate at higher temperatures. “In theory, a single dose vaccine would also be an improvement as all the current need two doses, but for technical reasons it is probably not possible while maintaining the same levels of protection,” said Prof Jones. Pharmaceutical giant Johnson and Johnson is, though, trialing an adenovirus-based vaccine that it hopes could be given as a single shot. Current clinical trials will indicate if just a single dose is enough. Other ways in which the current crop of vaccines could be improved on will emerge over time, according to Prof John Oxford, professor emeritus at the University of London and co-author of the textbook Human Virology . “We’ll learn from some of the weaknesses of the first generation,” he said. “There will be weaknesses. People raise questions: will they stop transmission? Can a person who’s been vaccinated still carry the virus and infect other people?” Scientists are analysing how the current vaccines will cope with emerging variants, including the more transmissible types first identified in South Africa and the UK. Multiple alterations to the spike protein, the part of the virus that attaches to human cells, and which antibodies recognise, may necessitate changes to the vaccine. BioNTech has suggested it could develop an amended version of its mRNA vaccine in just six weeks. “At some point in the future they may have to change the vaccines a little bit, but so far they’re still effective against the predominant variants,” said Prof Paul Hunter, an infectious diseases specialist at the University of East Anglia in the UK. “Pretty much every year the influenza vaccines change because there are new strains. With coronaviruses, they don’t mutate as rapidly. We may not have to [change] it for a while.” Including those already authorised by various authorities, 61 vaccines are in clinical trials and 172 in preclinical development, according to WHO. As well as mRNA vaccines and adenoviral vector vaccines, some jabs, like the Sinopharm vaccine being used in the UAE, are based on inactivated viruses that stimulate an immune response that provides protection against the coronavirus. Others that could be approved soon are made from purified coronavirus proteins. The immune response to these “protein subunits” – purified sections of the coronavirus incapable of causing disease – protects against the coronavirus. The adenoviral vectors approved so far, such as the Oxford-AstraZeneca jab, do not replicate inside the patient, but other vaccines coming on stream involve vectors that do multiply. Others being trialed are based on DNA rather than the mRNA of the Pfizer-BioNTech and Moderna vaccines. Of the large numbers under development, especially those at an earlier stage of the process, Prof Hunter said “most of them will fall by the wayside” because effective vaccines have already been created. “I would suggest many of these vaccines that are likely to fall by the wayside will work really well,” he said. One factor that may limit the development of additional vaccines is ethical approval for clinical trials, which typically compare one group who have the vaccine with another given a placebo. It is harder to justify giving vulnerable individuals a placebo when effective vaccines are already available. "If you have not done your randomised control trials by the middle of next year, you're probably not going to get it through ethics," said Prof Hunter. Nonetheless, the Coalition for Epidemic Preparedness Innovations (Cepi), a foundation formed in 2017 and supported by governments, philanthropists and organisations such as the Bill and Melinda Gates Foundation, has said funds are needed to develop “Wave 2” vaccines. Such vaccines may be easier to deliver – eliminating extreme cold-storage requirements, for example – and more suitable for particular groups, such as pregnant women, older people or people with weak immune systems. Cepi has nine candidate vaccines for its Wave 2 programme, each of which would ideally be protective after a single dose, easy to manufacture in large quantities and not require extreme cold storage. Cepi said in November it had raised $1.3bn to fund further coronavirus vaccine research, but needs a further $800m (Dh2.94bn) to fund the development of three vaccines that could be developed and made available by the end of 2021. The ultimate aim is to produce one billion doses by the end of 2022. In December, as part of the Wave 2 programme, Cepi announced it was contributing up to $10m to a South Korean company, SK Bioscience, for its genetically engineered protein vaccine. It consists of two components, a section of the coronavirus spike protein and a “core” particle to which it attaches. So, while immunisation has already started, the coronavirus vaccine landscape may change in the coming year as researchers look to overcome clinical, cost and distribution drawbacks of the current medicines. “You’re looking for greater stability, even higher efficacy and ease of storage,” said Prof David Taylor, a professor emeritus of pharmaceutical and public health policy at University College London, while acknowledging “it’s not very easy” for later vaccines to improve upon those coming to market now.

What to expect from the next generation of Covid-19 vaccines

Dozens of coronavirus jabs under development aim to be cheaper, easier to distribute and effective against different strains