In the face of the economic and social consequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) and the difficulties attendant in behavioral modifications that could slow progress of the disease (quarantine, lock-down, social distancing, frequent hand washing, and the use of facemasks), the world's best hope for a chance to return to normalcy is the development of an effective vaccine. The last disease against a virus for which a disease was developed was mumps (caused by Mumps orthorubulavirus) in the 1960's; that vaccine took more than four years to be developed. Even with the advances in immunology and virology in the 50+ years since that time, producing an effective vaccine less than 12 months after the outbreak of the SARS-CoV-2 pandemic would be (more hopefully, will be) a scientific triumph or a genuine miracle (depending on how one explains the unexpected).
As of August 13th, according to the World Health Organization (WHO), there are 29 candidate vaccines undergoing clinical evaluation, and another 138 candidates in preclinical studies. Those in Phase 3 studies include two based on inactivated viruses, from the People's Republic of China (Sinovac and Sinopharm, the latter being developed by the Wuhan Institute of Biological Products and the Beijing Institute of Biological Products). There are two RNA-based candidate vaccines: the Moderna/NIAID vaccine and the BioNTech/Fosun Pharma/Pfizer vaccine, both of which are lipid nanoparticle encapsulated RNAs. The candidate furthest along (by accounts in the press) is the University of Oxford/AstraZeneca vaccine, based on a non-replicating viral vector.
There are two vaccine in Phase 2 clinical trials: another non-replicating viral vector (Adenovirus Type 5) from the CanSino Biological Inc./Beijing Institute of Biotechnology, and a protein subunit vaccine from Anhui Zhifei Longcom Biopharmaceutical/Institute of Microbiology, Chinese Academy of Sciences. There are ten in Phase 1/2, including four DNA-based vaccines (from Inovio Pharmaceuticals/ International Vaccine Institute, Osaka University/ AnGes/ Takara Bio, Cadila Healthcare Limited, and Genexine Consortium), protein subunit vaccines (from Kentucky Bioprocessing, Inc. and Novavax), RNA (Arcturus/Duke-NUS) and non-replicating viral vectors (Janssen Pharmaceutical Companies), as well as a vaccine based on whole virion inactivation (Bharat Biotech).
The remaining 11 vaccines in Phase 1 include a vaccine based on a measles-based replicating viral vector (Institute Pasteur/Themis/Univ. of Pittsburg CVR/Merck Sharp & Dohme), a plant-derived virus-like particle (VLP)-based vaccine (Medicago Inc.) and non-replicating viral vectors (from Gamaleya Research Institute and ReiThera/LEUKOCARE/Univercells). Clover Biopharmaceuticals Inc./GSK/Dynavax is developing a "native-like trimeric subunit Spike protein vaccine," and Medigen Vaccine Biologics Corporation/NIAID/Dynavax has a protein subunit vaccine in Phase 1 clinical trials, while Vaxine Pty Ltd/Medytox is developing a vaccine based on a recombinant Spike protein formulated with Admax™ adjuvant. Curevac and the Imperial College of London have RNA-based vaccines in clinical trials.
Administration of these vaccines is almost universally intramuscular, typically requiring more than one dose where the doses are separated by 14-28 days (some with as long as 56 days between doses); the Oxford/AstraZeneca vaccine is effective with a single dose.
Of the 138 candidate vaccines in preclinical trials, 12 are DNA-based; 9 are inactivated virus; 3 comprise live, attenuated virus; 19 are non-replicating viral vectors, typically Adenovirus 5 or another adenovirus type; 50 comprise protein subunits, often the viral Spike protein; 17 are replicating viral vectors, using vesicular stomatitis virus, influenza virus, or other viruses; 16 are RNA vaccines, usually mRNA-based; and 12 comprise virus-like particles.
The incredible amount of time, money, effort, and intelligence behind these efforts are likely to produce a vaccine, particularly because this virus, unlike viruses that have proven intractable to vaccination stratagems, such as human immunodeficiency virus III, apparently does not mutate at a particularly high frequency, and its Spike protein provides the effector that binds to angiotensin I converting enzyme 2 (ACE2) in most species that can be infected (see "Sequence Comparisons Illustrate Susceptibility to Coronavirus Infection"). When the vaccine will be available is the question, and (to the frustration of politicians, leaders, and the general public) a frustrating one; the only thing perhaps even more frustrating is the fear that a significant part of the public will refuse to be vaccinated, producing an enduring reservoir of this disease resulting in a perpetual pandemic. Perhaps more rational heads will prevail on this issue, but if the past eight months are any guide this is becoming more and more unlikely, with parlous consequences for us all.
