Vaccine developers have advanced ten COVID-19 candidates into the clinic, less than 6 months since the SARS-CoV-2 virus was first sequenced. Leading candidates include an adenovirus-based candidate that is in a phase IIb/III trial and an mRNA vaccine that is in a phase II trial.

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The University of Oxford and AstraZeneca’s AZD1222, currently the most advanced COVID-19 vaccine candidate, consists of a chimpanzee adenovirus vector that has been engineered to carry the SARS-CoV-2 spike protein. Investigators hope that this vaccine will train the immune system to generate neutralizing antibodies against the spike protein, which the virus uses to bind and enter human cells. The immunogenic properties of the adenovirus vector could boost the potency of this approach. A 10,000-volunteer phase IIb/III trial is already underway in the UK, and a 30,000-volunteer trial is planned for the USA this summer.

Moderna’s mRNA-1273 is a nucleotide-based vaccine. A lipid nanoparticle carries the mRNA for the spike protein into cells, where it is then translated to provide an antigen for the immune system. A phase II trial of the vaccine is currently recruiting 600 volunteers.

No adenoviral vector or nucleotide vaccines have yet been approved by regulators in the USA or EU, however. Other candidates in clinical and preclinical development include protein subunit vaccines, which rely on purified spike protein to elicit an immune response, and whole-virus vaccines, which use weakened or inactivated forms of SARS-CoV-2 to confer protection.

Some vaccinologists are optimistic that hundreds of millions of doses of vaccines could be available for use within 18 months, or sooner. The USA’s Operation Warp Speed, for instance, is aiming for 300 million doses of a COVID-19 vaccine by January 2020. But, the historic precedent is daunting. The average development time for a vaccine is more than 10 years, and the probability of market entry for a preclinical candidate is 6%, found an analysis of vaccine development from 1998–2009.