The future of COVID-19 vaccines

Row of vials of future COVID-19 vaccines

On 12th January, 2020, China publicly shared the genetic sequence of the virus that causes what would come to be known as ‘COVID-19’.

Since then, eight vaccines have been fully approved for use in the fight against COVID, and a further nine are in early or limited use. Researchers are currently testing 95 potential COVID-19 vaccines in clinical trials on humans, and 32 have reached the final stages of testing.

But with several highly effective vaccines already in use, why is it important to keep working on and investing in vaccine development?

Having a range of COVID-19 vaccines accessible around the world is essential to bring the pandemic under control, because:

  • Any one vaccine will not be as effective or suitable for everyone: We often need multiple vaccines for a disease to be able to protect different groups of people.
  • Production needs to happen quickly and at scale: By developing and investing in multiple vaccine candidates we stand a much better chance of having the volume of doses we need to help contain the virus.
  • New technologies may improve vaccine accessibility: Dosing regime, storage requirements and manufacturing costs of current approved vaccines means there are inherent challenges to getting vaccines to everyone that needs them.
  • Some vaccines are more or less effective against new variants: Like any virus, COVID-19 will continue to adapt and mutate – having a range of vaccines in our armoury that utilise different technologies gives us the best chance for fighting infections.

With the unfortunate results of German produced vaccine Curevac, the world continues to search for more successful alternatives, and new hope emerges with Novavax which promises to compare against current successful mRNA vaccines. Dr Adrian Hyzler, Chief Medical Officer at Healix International, shares his outlook on the future of COVID-19 vaccines…

The promising: Novavax (protein subunit vaccine)

In June 2021, US pharmaceutical company Novavax announced strong results from a pivotal, 30,000-person, clinically diverse trial of its COVID vaccine that was carried out in the United States and Mexico. The two-dose vaccine uses a different technology to the currently authorised COVID vaccines. Instead, the vaccine delivers the spike protein itself, carried on nano-lipid particles along with an immune-boosting substance called an ‘adjuvant’. Protein technology has been used for decades in vaccines against diseases including hepatitis B and pertussis (whooping cough).

The trial data showed 90.4% overall efficacy against symptomatic COVID-19 infection and 100% protection against moderate to severe disease

The trial data showed 90.4% overall efficacy against symptomatic COVID-19 infection and 100% protection against moderate to severe disease, hospitalisation, and death. Furthermore, against eight viral variants of interest and concern, including ‘Alpha’ (the B.1.1.7 UK variant), the trial efficacy was 93.2%, however, only two Beta cases were sequenced within the cases. These results are similar to those reported by Novavax in January 2021 from a stage 3 clinical trial of more than 15,000 people in the United Kingdom. That trial showed the vaccine efficacy was 89% overall, 86% against Alpha, and 96% against the original virus strain. But in a separate trial involving 4,400 participants in South Africa, where Beta arose and was circulating widely, the vaccine’s overall efficacy sank to 49%. The question of vaccine immunity against Beta remains despite the promising data.

Novavax began to develop the vaccine in January 2020 and benefitted from $1.6 billion of the US government’s Operation Warp Speed. However, the company encountered production problems that delayed the launch of its North American clinical trial until late December 2020. Nevertheless, the results are phenomenally good, and they compare favourably with the stand-out mRNA vaccines from Pfizer and Moderna, despite the fact that those vaccines completed their trials before the variants were widely circulating. Novavax plans to apply for authorisation in the UK, EU, India, South Korea in Q3, and possibly the US, though the FDA has suggested that there are currently sufficient vaccine supplies and they would be looking more to a potential winter booster shot. Novavax has created a new version of its vaccine adapted to Beta that could be used as a 1-year booster. The vaccine has a good safety profile and is well-tolerated with reports of only minor side effects. Its simple storage requirements (it can be stored in a refrigerator for up to 6 months and, once removed, remain viable for 24 hours) could speed up distribution to remote communities around the globe. Novavax expects to reach manufacturing capacity of 100 million doses per month by the end of the third quarter and 150 million doses per month by the fourth quarter of this year. The company has already signed a deal to supply Gavi, the Vaccine Alliance, with 350 million doses for the COVID-19 Vaccines Global Access (COVAX) facility.

The resourceful: Cuban COVID-19 vaccines

Cuban scientists have developed four COVID-19 vaccine candidates rather than face the difficulties of joining the international COVAX initiative, which aims to deliver vaccines fairly across all countries. If they prove to be successful, Cuba will become the first Latin American country to develop and manufacture its own vaccine against COVID-19.

They claim that the triple-shot Abdala vaccine is 92.28% effective against SARS-CoV-2 in stage 3 clinical trials – no data have, as yet, been published. They also recently announced the Soberana 02 vaccine with a claimed efficacy of 62% in a 44,000 strong clinical trial. This is a ‘conjugate’ vaccine that links a weaker antigen with a stronger one to ensure a robust immune response. There are two other versions of Soberana vaccine, the 01 and the Plus, that both contain combinations of spike protein fragments. Cuba has just delivered its first batch of Abdala vaccines to Venezuela as part of a commitment to supply 12 million doses – advance payments will allow them to re-invest the resources into more production. Currently, Cuba is facing its worst outbreak since the start of the pandemic with record numbers of cases in the last 7 days, since re-opening its borders to tourism last November.

The disappointing: Curevac mRNA vaccine

Its two-dose vaccine, known as CVnCov, was just 47% effective at preventing disease

Shortly before Novavax announced their very upbeat trial data, the German biotech company Curevac released their eagerly awaited preliminary data from a 40,000-person trial, run across ten countries in Europe and Latin America. Disappointingly, its two-dose vaccine, known as CVnCov, was just 47% effective at preventing disease. There was a lot of hope riding on this mRNA vaccine, especially within the European Union, due to its relatively low cost and after age limits were introduced on both the Johnson & Johnson and AstraZeneca vaccines, owing to links to a rare but potentially fatal clotting disorder. It was also expected to last longer in refrigerated storage than the spectacularly effective mRNA vaccines made by Pfizer–BioNTech and Moderna. A year ago it was a frontrunner to produce the first effective COVID-19 vaccine and to expand the reach of mRNA-based vaccines to lower-income countries. Curevac negotiated a deal to provide the EU with up to 405 million doses of their vaccine. They projected manufacturing up to 300 million doses in 2021 and up to a billion doses the following year.

However, Curevac decision to develop a different type of mRNA chemistry to the other similar vaccines appears to have back-fired. mRNA is an incredibly fragile molecule and the challenge facing the vaccine developers is in preserving the integrity of the mRNA as it enters the body and makes its way into the cells. The Curevac method only allowed a relatively low dose of mRNA to be introduced, compared with the Pfizer/Moderna ‘modified mRNA’ technology, and this resulted in a relatively low level of neutralising antibodies – well below the levels seen in recipients of the Pfizer/Moderna vaccines, which are both given at higher doses. Curevac is poised to submit the final results of its late-stage trial to the EMA. The data show 53% protection against mild disease, 77% protection against severe disease and full protection against hospitalisation and death. Though this is better than the preliminary numbers, it still compares poorly with Pfizer or Moderna. The company argues that this should be viewed in the context of multiple variants that were not widely distributed during the early mRNA trials. In the meantime, in collaboration with GlaxoSmithKline, Curevac also has a second-generation COVID-19 vaccine in development that also uses unmodified mRNA but has been fine-tuned so that it elicits levels of neutralising antibodies that are around ten times higher in laboratory experiments. Human Phase 1 trials are due to launch later this year. The company is also working on a vaccine targeted at the viral variants in circulation, in partnership with Bayer, GSK and Novartis.

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