There has been a lot of talk about how “we” are making a lot of progress in creating a coronavirus vaccine lately, and it’s getting irresponsible. Yes, the Phase 1 and Phase 2 trials are going fine, but these tell us almost nothing about effectiveness. Phase 1 and 2 trials are meant to test a drug’s safety and to explore the effects at different dosing levels, but they are not useful in determining a vaccine’s overall effectiveness. Only the much larger, Phase 3 trials (usually randomized, blinded studies, in very large numbers of patients, studied over time) tell us how effective a vaccine will be in preventing a disease.
So far, we have all heard the press releases showing that Moderna’s experimental vaccine has shown an antibody response in 8 patients (yes, that was eight). First of all, 8 patients is nothing in terms of a clinical trial. It would have been more responsible to report that the Phase 1 trial showed that the drug was “safe enough to proceed on to further trials.” Second of all, showing an antibody response (in this case, production of “neutralizing antibodies”) does NOT tell us that these patients will be protected against infection. It is known that coronavirus infection causes production of multiple types of “neutralizing antibodies” (the June 2020 issue of Science magazine has an article documenting this) and it is not known what levels of which antibodies might be protective.
Viruses and bacteria often cause multiple types of antibody production, and the term “neutralizing antibody” implies that having it will prevent infection, but this is not necessarily true. Hepatitis B virus infection, for example, is known to cause production of multiple antibodies (to “core” antigen, “early” antigen, and to “surface” antigen) but only 1 of them (so-called “surface antibody”) demonstrates protection against the infection. This is also a problem with all of the antibody tests that received emergency approval from the FDA – no one knows what antibody will be protective, and they may all be measuring different antibodies. It is well-known that having a positive antibody test does NOT confer long-term protection in everyone who is positive.
There have been other vaccines (for example, an earlier version of Rotavirus vaccine, and most recently Dengvaxia, for Dengue virus) that were approved too quickly, and had very significant negative effects because they were not studied long enough in certain populations. The U.S. withdrew the earlier Rotavirus vaccine in less than a year, and the Philippines did the same with Dengvaxia after a huge number of pediatric deaths.
Additionally and most importantly, once a vaccine is shown to be safe and effective and approved for use, then it must be produced in huge volume and distributed to the world’s population. There is no quick way to make billions of doses of a vaccine, and it is almost certain that one will need 2 or 3 doses (or more), each separated by 1-2 months (or more) for adequate protection. Since more than 1 company, in more than 1 country, may develop effective vaccines, there will need to be international cooperation in licensing and distributing the vaccine(s). Everyone will feel that they are a priority. It is sure to get ugly, especially in this era of extreme nationalism and leadership by rant and tantrum.
The big message? 4-6 months (at best) until vaccine approval; 1-6 months to ramp up production/distribution; and 2 doses (at least) separated by 1 month (or more). That means reasonably a full year before anyone gets a second dose.
P.S. There aren’t even any trials testing the vaccines against children yet…