Developing Covid-19 Vaccines at Pandemic Speed - NEJM
Bron: 30-3-2020; https://www.nejm.org/doi/full/10.1056/NEJMp2005630By: N. Lurie
Describe the pitfalls of developing vaccines rapidly
- CEPI (coalition for epidemic preparedness inovation) is an international nongovernmental organisation that aims to develop reserves of investigational vaccines for each pathogen after such vaccines have completed phase 2a trials, expecting that they will undergo clinical trials during future outbreaks. In addition; it aims to develop a platform to prepare for “disease X”, an unknown newly emerging epidemic disease (like covid-19).
- An ideal platform would support development from viral sequencing to clinical trials in less than 16 weeks and afterwards be ready for mass manufactering.
- Especially DNA- and RNA based vaccines can be quickly made.
- Use of next-generation sequencing and reverse genetics may also cut development time of more conventional vaccines during epidemics.
- SARS-CoV-2 vaccine development poses challanges:
- Debate on the ideal immunogen
- Second, preclinical experience with vaccine candidates for SARS and the Middle East respiratory syndrome (MERS) have raised concerns about exacerbating lung disease, either directly or as a result of antibody-dependent enhancement. Therefore rigorous safety monitoring in clinical trials is essential.
- The duration of potential duration of immunity is unknown
- Vaccine development is lengthy and expensive, for a pandemic quick development is needed. Therefore several steps need to be taken simultaneously, leading to additional costs. (see figure)
- CEPI started vaccine development as soon as the first covid cases in Wuhan. Development is proceeding quickly:
- a phase 1 clinical trial started on march 16
- Phase 2 studies are being prepared, which means manufacturing will need to be scaled up quickly to reach commercial levels (even before safety and immunogenicity data are available..) which is very costly. This is however very difficult to finance since its effectivity is not even known.
- Moreover; in a high-mortality situation populations might not accept placebo controlled trials
- CEPI has not yet established financial mechanisms to support the development of pandemic vaccines and will need to raise additional funds to see SARS-CoV-2 vaccines through development and manufacturing processes.
- Globally fair vaccine-allocation systems need to be set up.
- Though it’s unlikely, if the pandemic appears to abruptly end before vaccines are ready, we should continue developing the most promising candidates to a point at which they can be stockpiled and ready for trials and emergency authorization should an outbreak recur.