No Cutting Corners: Vaccine Expert Answers Questions From Public, Clinicians

With Russia recently announcing the surprise approval of a vaccine that hasn’t been through the usual safety testing process, and the US accelerating its own vaccine development program through Operation Warp Speed, vaccine development and distribution is clearly a major part of the international strategy to curb the coronavirus disease 2019 (COVID-19) pandemic.

Our recent “COVID-19: Race for a Vaccine” webinar debuted on July 30, 2020. Click here to register and watch the program on-demand.

This webinar featured top minds in the field including:

• Walter A. Orenstein, MD
• Angela Rasmussen, PhD
• Gregory A. Poland, MD

Our panel answered audience questions during the program. Now, Dr. Orenstein, the moderator of our discussion, answers some of the audience questions that we didn’t get to during the live program.

Q: How can we measure the efficacy of a vaccine? Like flu, the coronavirus may mutate.

Answer: Efficacy is defined as the difference in the incidence rates of a disease in those who are vaccinated versus those who are not.

The formula for calculating vaccine efficacy (VE) in % is (ARU-ARV/ARU) X100, where ARU is the incidence rate in those vaccinated and ARV is the incidence rate in those not vaccinated.

Following the availability of vaccines for use, it is critical to have a system in place to conduct surveillance of COVID-19 and determine whether cases are in vaccinated people or not. This will allow calculation of vaccine effectiveness, and if VE is low, one can then determine the cause of the decrease such as mutation of circulating viruses, waning immunity, poor storage of vaccine, etc.

Q: Will a rushed vaccine be a cause for concern of more or perhaps more severe side effects?

Answer: It is critical to assure vaccines are safe. No corners should be cut.

It is important that information on safety and efficacy be reviewed, in my opinion, by the US Food and Drug Administration (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) in open session so the pubic can understand the safety data.

Regardless of the results of the clinical trial, there will be a need to continue to monitor safety, especially once FDA has approved the vaccine and it is in use in the country. This means you should report adverse events to VAERS, the Vaccine Adverse Event Reporting system, and that FDA and CDC should do studies, when appropriate, to determine if the adverse event is causally related or only coincidentally related. More information on the monitoring of vaccine safety can be found at the following CDC website:

https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/

Q: Some have expressed hope for a vaccine that is over 90% effective. Is this plausible?

Answer: Even an efficacy of 50%, the minimum for a vaccine that FDA would consider approving, is much better than 0%, which is what we have now.

Certainly, we would all want a vaccine that is over 90% effective. Preliminary immunogenicity data are very encouraging for several of the vaccine candidates. But While a 50% VE would not terminate transmission, it would markedly reduce it.

Q: Allowing a vaccine with only 50% effectiveness could damage public acceptance for future coronavirus vaccines. How do we get around this?

Answer: If I am vaccinated with a 50% effective vaccine, it is in my self interest to urge all members of my family, my neighbors, my friends, my colleagues and others to also get vaccinated which will decrease my chances of getting exposed to someone who is an active transmitter of SARS-CoV-2, in case I among the 50% of vaccine recipients not protected.

A 50% effective vaccine is still a lot better than a 0% effective vaccine, which is what we have today. If the average case of COVID-19 transmits to 3 people in a 100% susceptible population (an Ro or 3), then if we could achieve 50% immunity in the population, then the average transmitting case would transmit to < 2 people, curtailing transmission.

Q: Since most of the people dying of COVID-19 are over 70 years of age, why would they not be the first to be vaccinated , even over essential workers who are not at high risk based on age and absence of predisposing co-morbidities?

Answer: It is critical to protect our healthcare workforce.

If they do not come to work because they get sick, who will take care of all of the other patients in the hospital or visiting health clinics? Also, there is the possibility if they are infectious but asymptomatic, they could infect high risk patients. Other workers may also be essential for keeping society going. Certainly, the elderly would likely receive a very high priority for vaccines but probably after healthcare workers. The prioritization issue is being addressed by a Committee formed by the National Academy of Medicine. Further the Advisory Committee on Immunization Practices (ACIP) of the CDC is the group most likely to recommend priorities when vaccine supply is limited.

Q: What is the ethical way to distribute the vaccine groups of people? How do we protect/vaccinate the minority population that is being hardest hit and won't be able to pay for it? What is the ethical way to distribute the vaccine groups of people?

Answer: The National Academy of Medicine (NAM) has formed a committee to evaluate priorities for vaccination, which will consider potential priorities for high risk groups, such as racial/ethnic minorities.

The CDC’s Advisory Committee on Immunization Practices (ACIP), usually the major source of vaccine recommendations is also considering priorities.

Critical to assuring groups which have high priority for vaccines actually receive them, is removing barriers to access. This should include elimination of economic barriers to access (ideally free vaccine for all), access barriers (convenient locations and hours) and more. The CDC is likely to coordinate the vaccination effort, drawing on experiences with the 2009 H1N1 influenza pandemic vaccine distribution.

Q: If you are over 65 years of age with medical conditions, should you wait 3-4 months after the drug is licensed?

Answer: I would recommend that if you are in a priority group as defined by CDC’s ACIP, that you get vaccine as soon as you can. Prioritization to the elderly, especially those with medical comorbidities is likely, if the pre-licensure data show the vaccine is safe and effective in this group.

The reason this group is likely to get high priority is they are at substantially greater risk of complications of COVID-19 than the general population.

Q: Once COVID-19 vaccines become commercially available do you anticipate the general population will be mandated to receive them or will they be voluntary based on the individual patient need or religious beliefs?

Answer: Efforts will be to achieve voluntary acceptance the groups prioritized for vaccines.

It is up to all of us to encourage acceptance of vaccines not only for that person's health but also for society’s health including our own health by leading to immunity levels that terminate or markedly reduce transmission.

Q: Should high risk patients obtain a flu vaccine and pneumonia vaccine?

Answer: Yes.

It is particularly critical to get both vaccines in persons for whom the vaccines are indicated to protect from both diseases, decrease the burden on the healthcare system, and prevent superinfection of someone with COVID-19, which is likely to very adversely affect the prognosis.

Q: What is the relationship between vaccine and herd immunity?

Answer: Vaccines protect in two ways.

First, they induce an active immune response in the vaccinee, which prevents that vaccinee from getting disease if exposed.

Second, they protect indirectly by inducing herd immunity or community protection.

The vast majority of vaccine-preventable diseases are known as person-to-person spread diseases, including COVID-19.

A transmitting case comes in contact with a susceptible person and transmits infection. After an incubation period, the newly infected person becomes contagious and transmits infection to susceptible persons he or she comes in contact with. This leads to a chain of human-to-human transmission.

When a transmitting case comes in contact with an immune individual, no transmission takes place and that chain of transmission is broken.

Who are the people indirectly protected because they are not exposed? They are persons for whom vaccine is not recommended, such as children too young, persons with legitimate medical contraindications, those with impaired immune systems, and more.

In fact, since no vaccine is 100% effective, even some vaccinees may be susceptible and indirectly protected because they are not exposed to the pathogen.