The entrance to the patient testing facility of the Operation Warp Speed vaccine trial at Joint Base San Antonio-Lackland, Texas. Operation Warp Speed is a partnership to accelerate the development, manufacturing, and distribution of COVID-19 vaccines. (Photo by Airman 1st Class Melody Bordeaux/59th Medical Wing.)

The DoD will have an independent, but collaborative, program with the U.S. Department of Health and Human Services (HHS) and the Center for Disease Control (CDC) to provide COVID-19 vaccines to DoD uniformed service members, both the active and Selected Reserve components, including members of the National Guard; dependents; retirees; civilian employees, and selected DoD contract personnel as authorized in accordance with DoD regulation. The Department’s priorities are protecting our Service members, DoD civilians, and families; safeguarding our national security capabilities; and supporting the whole-of-nation response to the COVID-19 pandemic.

Dr. Limone Collins, Jr., chief of vaccine safety and evaluation at IHD, talked to MHS about the development and clinical trials process of the vaccines.

MHS: What role has IHD had in the COVID-19 vaccine development?

Collins: This is a collaborative effort consistent with how we do things within the DOD. It’s not just IHD – we had a contributory role, but this effort couldn’t have been accomplished without a number of folks within the DOD to make this happen. Our primary role in IHD is to serve as consultants and guides to immunizations within the DOD based on our knowledge and our familiarity with respective points of contact, the variety of military medical treatment facilities, and the procedure itself. It was based on our experience collaborating with the Infectious Disease Clinical Research Program out of the Uniformed Services University of the Health Sciences with a multi-site study looking at the effectiveness of the different types of the influenza vaccine that helped us, particularly within IHD as well as IDCRP, to really know the lay of the land and to help serve as consultants to make the DOD’s role in this even smoother.

MHS: How is a vaccine like this, to counter the SARS CoV2 virus, developed?

Collins: There are a variety of vaccine types but the primary types that have gone to EUA [emergency use authorization] are called messenger RNA [ribonucleic acid] (mRNA)-type vaccines. The DOD is involved with what is called a viral vector-based vaccine. The whole thought process is to see how we can manipulate the immune system to get the most effective vaccine. It has been taken up by a number of the manufacturers early on in the hypothesis to see what type of vaccine we are going to be looking at to try to accomplish the ultimate goal of having an effective vaccine.

MHS: How was it able to be developed so much faster than other vaccines?

Collins: There had been some research, particularly based on our experience with the Ebola vaccine and dealing with SARS [Severe Acute Respiratory Syndrome] and Ebola, so that was helpful. But there are also new constructs in regard to how we develop vaccines. The utilization of different technologies contributed to our ability to move at a more rapid rate, and the combination of the veering phases that we would generally go through also helps. It was a combination of all these things: newer technologies, looking at our past experience with similar organisms, as well as combining the typical phases that we generally go through.

MHS: How many steps/phases comprise a vaccine trial and what occurs in each?

Collins: The classic answer is that there are four phases. The first phase, which some folks call Phase 0, is when you start developing your hypothesis: What type of vaccine are we looking at? And that’s when you consider whether we’re going to have an inactivated vaccine, use the mRNA technology, or a viral-vector vaccine? What are we looking to accomplish with the vaccine we’re proposing? That is followed by looking at a smaller group of individuals, generally less than 100 healthy folks, to look at the safety of the particular vaccine. Then you go to the next step (Phase II), where you have a larger group of individuals, again looking at the safety and the effectiveness. Then you get to where most of the vaccine trials currently stand, which is Phase III, where you have a large trial of individuals (within the 30,000 or 40,000 range) focusing on the efficacy of the vaccines. That is followed by Phase IV, where you’ve done your large trials, sent it to the FDA for analysis and their determination that your vaccine has met all its goals and is an efficacious as well as an effective vaccine.

What most people don’t realize is that even after you get licensing by the FDA there is a follow-up period, what we call a post-surveillance activity, which basically continues with the evaluation of a vaccine or drug, where you continue to observe them for their safety precautions. This is particularly important because now you’re putting it into the general population, so it becomes even more important to look at whatever safety signals may come when you put it into that general population.

MHS: How long is that follow-up observation period once it’s distributed among the general population?

Collins: All those things were determined by the FDA during their analysis – they make the final decision on the length of the post-surveillance time period. There could be contributory information that the Advisory Committee on Immunization Practice may also try to solicit in regard to that post-surveillance time period.

MHS: What is the process of recruiting volunteers for vaccine trials?

Collins: That’s particularly important with regard to this vaccine. A lot of it is determined by the scientists of the manufacturers in their initial proposal. It’s particularly important for the COVID-19-related vaccines based on what we’re seeing in regard to the epidemiology, what’s happening with the disease manifestations, its morbidity and mortality.

MHS: Was there any special effort to include military service members to volunteer for the trials?

Collins: All the volunteers in the AstraZeneca trials, in which the DOD is participating, are DOD beneficiaries. When the company approached the DOD, we looked at who would be captured by our variety of military medical treatment facilities, so although the initial conversation considered folks outside DOD beneficiaries, in order to really help facilitate the logistics, such as access to military facilities, it was decided that we would focus primarily on DOD beneficiaries. Trying to incorporate individuals who didn’t have that usual access to our facilities or to onboarding our clinics, etc. would have been a bridge too far, particularly when considering the time frame we had, so that’s why it was limited to military service members.

MHS: When people hear in the news that a vaccine candidate is at 90 or 94 percent efficacy rate, what does that mean?

Collins: To put it in simple terms, it’s a percentage of reduction in disease in the vaccinated group versus or compared to those who are unvaccinated.

You have different arms: Individuals who were vaccinated with the product and individuals who were given a placebo. But it’s blinded, so neither the individuals nor the investigators know whether a particular volunteer is getting the vaccine or a placebo. Then, the individuals from both arms go out into their environment where there’s a potential for them to be exposed to COVID-19. The investigators then look at the number of people from the vaccinated group who got COVID-19 versus the number from the group that received the placebo that got COVID-19. For example, out of 100 people who were vaccinated maybe five got COVID-19 versus the group of 100 folks who got the placebo of which maybe 50 developed COVID-19. That’s how you do your comparison and arrive at the efficacy rates.

MHS: Does getting a vaccine prevent the person from contracting the disease, or does it cause their symptoms to be less severe if they get it, or both?

Collins: Now you understand precisely the importance of why we need multiple vaccines, because they work differently. It’s also why we need to continue to observe what occurs with each individual vaccine and the epidemiology.

What we think may happen is some of the vaccines may do more mitigating. For example, if you take a flu shot you may contract the virus, but abort the symptoms, that is, you may have milder symptoms such as fever or nasal congestion. In that circumstance, you mitigated some of the sequelae or symptoms associated with influenza the disease. That’s what we’ve seen periodically with utilizing a variety of the influenza vaccine, particularly. There are years where we have “better” flu years or seasons than others; that’s because the development of the influenza vaccine for that year did more mitigation than eliminating the disease.