Vaccines For SARS-CoV2

Vaccines are the greatest public health advance in human history. From the dawn of civilization, humans living in large groups in one place have presented the microbial world with tempting targets to exploit. The past is replete with the stories of diseases such as smallpox which took many millions of human lives every year. The advent of vaccines for smallpox, polio, measles and other viral diseases has made humanity safer and markedly reduced morbidity and mortality.

We now talk about emerging infectious diseases like Covid-19. The world population is now 7.8 billion people. Humans come into contact constantly with unique viruses that exist in other species; some of these viruses can jump from their native species to us. This happened with SARS-CoV-2 in Wuhan, China in late 2019. Because humans congregate and travel ever more rapidly around the planet, the virus has now spread to 176 countries and regions, with a total (as of 27 March) of 566,269 reported cases and 25,423 deaths. The need for an effective vaccine grows more acute with each passing day.

 Fortunately, we live in a time when molecular biology is far enough advanced to help deliver vaccines. The Chinese scientists who isolated this virus sequenced the genome and made it internationally available 11 days after notifying the WHO of the outbreak in Wuhan. The genome sequence is critical because there are many labs worldwide that have developed a variety of platforms to generate a vaccine using that knowledge. Rather than only the older methods of growing virus, inactivating it, and making vaccine, there are now multiple avenues to proceed on to vaccine development. This does not mean that every approach will be fruitful but it certainly expands the options and may compress the timeline for viable vaccine candidates to test.

 Currently, there are at least 20 vaccine candidates for COVID-19. Two have entered trials. Moderna, a biotech firm in Connecticut, delivered a candidate vaccine based on messenger RNA to NIH on 24 February. A Phase 1 trial began in Washington State on 16 March. Another candidate vaccine is enrolling subjects in Wuhan, China; that vaccine is based on a modified adenovirus carrier that does not cause disease. The other vaccine candidates are in preclinical evaluation; they are being developed by small biotech firms as well as large pharmaceutical companies such as Janssen and Sanofi. There are also governmental agencies such as BARDA (Biomedical Advanced Research and Development Authority, a part of HHS) which are engaged alongside laboratories at the National Institutes of Health in Bethesda, Maryland. The global effort for vaccine development is funded by organizations such as CEPI (Coalition for Epidemic Preparedness Innovations) which bring together private foundations, governments, and investors to seek a successful vaccine for this pandemic disease.

 How soon will a vaccine be available? As many esteemed infectious disease experts have stated repeatedly, the time to a deployable vaccine will likely take upwards of 12 to 18 months. The reasons for this are multiple. Vaccines like all therapeutic modalities must be both safe and effective. Over many years of vaccine research, there have been vaccines that were abandoned or never brought to fruition because of safety or efficacy reasons. The process to test vaccines goes through multiple phases. The first phase is animal testing. Because of the rapidity of spread of COVID-19, that phase was not done with the two vaccines currently in human testing. That is itself a gamble but one made with the knowledge of the type of vaccine platforms being used.

Human testing begins with Phase 1 trials. A small number of healthy subjects receive the candidate vaccine and are observed for enough time to assess immediate safety. Usually, these trials take at least 2 to 3 months to complete. In addition to safety, the subjects have blood drawn to assess if they have developed antibodies that may be protective. In Phase 2 testing, a larger number (several hundred) of subjects receive the vaccine candidate; these are also healthy people and the primary purpose of this phase is to better understand safety. The larger number of subjects allows for more dose options to be administered and blood is also drawn then to evaluate how dosing might affect immunity. Phase 2 testing also takes 2 to 3 months but may go longer. Phase 3 testing then extends the process to perhaps thousands of subjects with a wider age range and also medical conditions that would not have been allowed during the earlier phases. More safety and immunologic data are gathered but now the goal is to see if vaccinated subjects show protection in the real world, i.e., is the candidate vaccine protective and if so, to what degree. Phase 3 testing usually takes 1 to 4 years.

Why so long? The safety problems being looked for maybe immediate (allergic reactions) or delayed. In the past, delayed problems included neurologic issues such as Guillain-Barre syndrome and intussusception with early rotavirus vaccines in children, where months may elapse before the complication is noted. There is also the possibility that the immune response to a vaccine candidate may provoke increased susceptibility to morbidity or mortality rather than protection. Finally, everyone must be aware that such trials are done with human subjects. Researchers have an ethical duty to protect these subjects from harms as far as those harms are understood.

 Hopefully, this will help you understand the challenges inherent in developing, testing, and deploying vaccines. In the interim, public health measures to prevent the spread of COVID-19 (handwashing, physical distancing, quarantine) are paramount to prevent our medical system from being overwhelmed and to buy the time that is needed for a vaccine solution. A large dose of patience and forbearance is indicated for all of us.

 Feel free to send questions and concerns about COVID-19 and this pandemic to healthcare [at] LWV-PA.org. They will be collated and addressed in future columns; individual answers to individual questioners will not be provided. Please stay safe and don’t forget to wash your hands, stay 6 feet away from others, and, as much as humanly possible, don’t touch your face.

Dr. Thad Zajdowicz is the Co-Chair of the League of Women Voters-Pasadena Area Healthcare Committee and a retired infectious disease physician who spent many years in clinical practice and emergency preparedness and pandemic planning for the US Navy. He holds a Doctor of Medicine degree from the Temple University School of Medicine and a Master of Public Health degree from Old Dominion University/Eastern Virginia School of Medicine.