September 4, 2020

expert reaction to a study looking at two open, non-randomised phase 1/2 clinical trials of the Russian rAd26 and rAd5 vector-based COVID-19 vaccine

A study, published in the Lancet, looked at two open, non-randomised phase 1/2 clinical trials of the Russian rAd26 and rAd5 vector-based COVID-19 vaccine.

Prof Eleanor Riley, Professor of Immunology and Infectious Disease, University of Edinburgh, said:

“Scaling up vaccine production at this stage is not unreasonable; we are doing the same here with the Oxford and Imperial College vaccines and you need to begin to scale up in order to have enough vaccine to conduct a large phase 3 trial. The key question is whether the next step for this vaccine is indeed (as we would expect) a randomised, blinded, placebo controlled phase III trial or whether the vaccine developers will come under political pressure to release doses of vaccine for administration to the general public.  The approval granted for the vaccine  – apparently under a law introduced after the onset of the pandemic – allows for both.

“Whilst the wish to protect high risk groups is understandable, there are existing effective public health measures for achieving this in the short to medium term. A vaccine should not be used to short-cut the implementation of public health interventions that are already known to be safe and effective until the vaccine itself has been shown to be safe and effective. Populations at highest risk of severe disease and death from COVID-19 (the elderly and those with underlying health conditions) are also those least likely to respond effectively to the vaccine and any adverse effects associated with vaccination may also be more likely in these populations.”

Dr Ohid Yaqub, Senior Lecturer at the SPRU (Science Policy Research Unit), University of Sussex, said:

“Normally, such a study would be the basis for debating whether to proceed into larger trials and the costs that entails. In that context, the study results are encouraging in terms of safety and possible efficacy.

“However, in the context of regulatory approval, the design and size of a phase 1/2 study is not anywhere near sufficient for widely recognised standards of approval. The study was not randomised, and it was not large enough to detect rarer safety issues.

“Further work, and its full and open disclosure, is to be encouraged. We would benefit from multiple vaccines with different manufacturers and with different attributes. For example, the design of a more thermostable candidate could be particularly valuable for parts of the world that are difficult to reach.

“That said, there are considerable benefits of co-operating in head to head trials, since they would make it easier to evaluate which vaccine candidates to roll out in which situations.”

Prof Brendan Wren, Professor of Microbial Pathogenesis, London School of Hygiene & Tropical Medicine, said:

“The data on the Russian vaccine studies reported in the Lancet are encouraging – demonstrating the safety and immunogenicity of the adenovirus-based COVID-19 vaccines. The results are unsurprising as the Oxford group have also shown similar adenovirus-based vaccines do not produce major side effects in humans and that immunological responses to the Spike protein are observed. The study is undertaken to a good standard on 76 subjects up to 60 years of age, so it is not proven in the very elderly where the vaccine is most needed. Given that the development of a COVID-19 vaccine is a global imperative, it is sensible to register the vaccine and to start production, as is the case with the Oxford vaccine. The report is a case of “so far so good”, but immunological responses may not necessarily evoke protection and further investigation is needed on the effectiveness of this vaccine for prevention of COVID-19.”

Prof Ian Jones, Professor of Virology, University of Reading, said:

“The study confirms what has been seen with Adenovirus vectors elsewhere, that they are generally safe and that they generate an immune response to the Sars-CoV-2 protein that is incorporated. While the numbers are relatively low the double serotype approach seems to have generated good levels of neutralising antibodies and T-cell activity. What everyone wants to know is if this translates the protection in the field and the recently announced phase 3 trials should provide that.”    

Dr Michael Head, Senior Research Fellow in Global Health, University of Southampton, said:

“This manuscript confirms some of the public statements from a few weeks ago, namely that this appears to be a promising vaccine candidate. Phase 1 and phase 2 trials have been carried out, and there is sufficient reason to scale up into much larger phase 3 trials. That would be the right way to go about vaccine development R&D. Concerns do remain around some of the previously-made ambiguous comments that this vaccine is about to be formally approved and licensed. At this stage, we do not know if the vaccine actually works – that is what the phase 3 trials will tell us. Public confidence in any licensed vaccine is vital, and suggestions from both Russia and the USA that a vaccine may be fast-tracked without the proper research having taken place are problematic. We must be open and transparent about the effectiveness and safety profiles of all vaccine candidates. Ultimately, we must not pour additional fuel on the anti-vaccine lobby fires.”

‘Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomised phase ½ studies from Russia’ by Logunov et al. was published in The Lancet on Friday 4^th September at 12:00 Midday UK time.

DOI: 10.1016/S0140-6736(20)31866-3

All our previous output on this subject can be seen at this weblink:

www.sciencemediacentre.org/tag/covid-19

Declared interests

Prof Eleanor Riley: No conflicts of interest to declare

Dr Ohid Yaqub: No conflicts of interest to declare.

Prof Brendan Wren: No conflicts

Prof Ian Jones: No conflicts

None others received.