A scientist’s opinion : Interview with Professor Johan Neyts about COVID-19 vaccines

Johan Neyts is full professor of virology at the University of Leuven, Belgium. He teaches virology at the medical school and at the school of dentistry. His lab is deeply involved in the development of antivirals against SARS-CoV-2. A second focus of the lab is the development of novel vaccine technologies. To that end, the yellow fever vaccine is being used as a vector. Using this technology, his team has developed a potent single-shot SARS-CoV-2 vaccine candidate, RegaVax. Johan Neyts is a past president of the International Society for Antiviral Research. Four classes of antivirals discovered in his laboratory have been licensed to major pharmaceutical companies (two for hepatitis C, one for dengue and one for rhino/enteroviruses). He has published more than 500 papers in peer-reviewed journals and has given around 230 invited lectures. He is regularly interviewed by the media.

What is the main difference between RegaVax and other vector vaccine candidates, and when do you envisage that it will be available to the public?

Johan Neyts: RegaVax is a platform technology to design and produce live-attenuated recombinant vaccines vectored by the original yellow fever vaccine (YF17D). The YF-vaccine is one of the oldest, most widely used and most efficient vaccines. One single dose results rapidly in life-long protection. As such, the YF vaccine serves as a vehicle, or vector, for a foreign target antigen (Antigen of Interest, AOI). This AOI is derived from a pathogen to which an immune response, such as an antibody response, needs to be mounted for the purposes of immunisation. For example, with SARS-CoV-2, the AOI is the spike protein. The YF17D vaccine delivers the AOI inside the vaccinated individual and triggers an immune response towards this antigen.

A big advantage is that RegaVax vaccines protect not only against the foreign pathogen for which the antigen has been inserted (for example SARS-CoV-2), but are also highly efficacious against yellow fever. The outstanding potency of the original YF17D legacy vaccine also translates into vigorous immunity against the transgene and confers full protection against aggressive infection challenge with such viruses. Our YF17D/Covid vaccine candidate prevents infection with SARS-CoV-2 and confers protection against lung disease after a single dose in hamsters [Sanchez-Felipe et al., Nature (2020)].

Furthermore, the vaccine induces a fast and long-lasting immunity, a humoral, balanced polyfunctional cellular and strong innate response, and shows an excellent safety profile, so very good tolerability.

Using the same technology, we are also developing other vaccine candidates. Our YF17D/rabies candidate protects mice, after only one dose, against both lethal rabies and stringent yellow fever challenge. Note that current rabies vaccines use three to five doses. On top of that, our YF17D/Zika vaccine results in spectacular and full protection of pups against direct intra-placental challenge with Zika virus in vaccinated mice [Buh Kum et al., Nature PJ Vaccines (2018)] and results rapidly (in approximately seven days) in high titers of neutralising antibodies in non-human primates and subsequent Zika challenge (unpublished).

A contract development and manufacturing organisation is working on process optimisation and good manufacturing practices for production. The hope is to have this vaccine approved in 2022.

Results of the phase III trials of the Oxford ChAdOx1 nCov-19 vaccine show an overall vaccine efficacy of 70.4%. Taking into consideration the reported 90% efficacy of the Pfizer/BioNTech vaccine, do you believe this difference could lead to misconceptions and a loss of public confidence in vector vaccines, and if so, how can people be assured that the quality of all Covid-19 vaccine candidates meets European and international standards?

Johan Neyts: The AstraZeneca vaccine was approved with an ‘official’ efficacy rating of 62%. New data reported by the company shows that a longer interval between the first and second doses results in a marked increase in efficacy, of up to around 80%. The Sputnik V vector-based vaccine has an efficacy of above 90 %; the overall efficacy of the Johnson & Johnson vaccine is comparatively lower at 66%, but good protection against severe disease is observed (83 %). Importantly the J&J vaccine is given as single dose. A two-dose phase III study is running. It can be anticipated and hoped that the efficacy will increase following a second dose. A longer interval between the first and second doses may also further increase the efficacy of this vaccine.

My view on the whole situation is that it is also possible with vector-based vaccines to obtain excellent protection. Fine-tuning of doses and dose schedules may have a further, marked positive impact on efficacy. Obviously, the earlier reported efficacies may indeed lead to misconceptions in relation to public confidence. It is of the utmost importance that the wider public understand that the authorities that approve vaccines (that is the EMA for the EU) are independent experts that do a deep dive into the data and make a decision based on the vaccine’s safety profile and efficacy.

It is also important that the public understand that it is most remarkable that efficacious to very efficacious vaccines have been developed in just one year’s time and that this was not a given. In the spring of 2020, the general hope was that the first vaccines would be available by the summer of 2021. We should also aim to communicate to the public at large that it is logical that not all possibilities for dosing and vaccination schedules could have been explored in a time span of one year, as would have been possible in a normal, longer development process, and thus that one may expect that more optimal dosing and dosing schedules may be suggested based on new studies in the coming months. This should and will hopefully result in well-deserved and much needed trust in these vaccines.

In your opinion, can there be any cross-reactivity against the SARS-CoV-2 in vector vaccines (especially RegaVax) and if so, can we expect them to be effective against new coronaviruses and other diseases in the future? Can mRNA vaccines be effective against new coronaviruses and other diseases in the future?

Johan Neyts: I am not sure that I understand exactly what you mean with ‘cross reactivity’; possibly you are referring to the vaccines’ effectiveness against variants. For variants, that remains to be seen. For the approved vaccines, but also for RegaVax, protection against the UK variants is comparable to protection against the Wuhan strain. Clinical studies with the Novavax and J&J vaccine in regions where the South African strain was circulating demonstrate some reduced efficacy.

In general, the vaccines should not be expected to be active against new coronaviruses that may possibly emerge in the future. If new viruses emerge, whether belonging to the coronavirus family or not, new vaccines will need to be developed each time. In such cases, new drugs, together with quarantine measures, may help to contain new viruses in the weeks after they emerge. They can be used to treat patients as well as for the prophylaxis of the healthcare workers that take care of them, and their close contacts. The messages sent to the human cells by both vaccines are the same, it is only the way in which that code is introduced that differs.

Misinformation about the capacity of mRNA vaccines to transcribe or modify human DNA is circulating online. How can the general public be assured of the facts?

IJohan Neyts: t will be important to develop easy to understand messages or animations for the wider public. To this end, popular influencers may need to be involved. Experts should help the media and influencers to develop a story that is easy to digest.

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