Vaccination and the immunocompromised population – an interview with Deepali Kumar

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In this interview we speak to Deepali Kumar (University Health Network and University of Toronto, Canada) about vaccination in the immunocompromised population, including guideline updates, understanding immunology and the future of this field.

First, could you just introduce yourself and just tell me a bit about your background?

My name is Deepali Kumar, and I am an Infectious Disease Physician in Toronto, Canada. I work at the University Health Network and University of Toronto, and I am a Full Professor of Medicine.

Ever since I started working fully after training, my research interests have been in infections of the immune compromised. Specifically, I focus on vaccinations and vaccine responses in immunocompromised patients, including in solid organ transplant patients and in stem cell transplant patients.

As part of that, I have been involved in guideline development on vaccinations; I have been a member of the Canadian National Advisory Committee on Immunization in the past and I have been involved on various levels in policy creation on vaccination. I have a lab as well as a clinical research program and we primarily do translational research. For example, we take blood samples from patients, bring them back to the lab and look at their immune system in response to the vaccines they have received.

Why is it important to understand the use of vaccines in the immunocompromised host?

I think immunocompromised hosts are a unique population that allow us to learn about vaccine-preventable diseases as well as how vaccines work on the immune system. For example, immunocompromised hosts are in general more susceptible to vaccine-preventable diseases, and they will get more severe disease.  Clearly, this is not good for the patients, but it is a good population to study the effect of vaccination because you have more disease outcomes. Immunocompromised hosts are very vulnerable. For example, in the context of influenza infection, they have been called super-spreaders and super-shedders – they shed the virus for a long time, and they harbor higher levels of virus so can be very contagious as well. Trying to learn more about how influenza vaccine works in that setting is very important. We need to understand the mechanisms of vaccine response in order to develop better vaccines for these patients.

It is also a good population to study immunology of vaccines, for example, if an organ-transplant patient is on a specific anti-rejection medication, such as mycophenolate, you can actually study the effect of that specific medication on vaccine response in vivo and learn a lot more about the immunology of the vaccine that way. If you knock out specific B- or T-cell pathway, will the vaccine still have an effect? Learning how specific immunosuppressives impact vaccine responses is a great way to learn about the immunology of vaccines.

Could you outline some of the current big gaps in our knowledge for this group and vaccinating them?

In the past, we have not had a lot of data on the immunogenicity, effectiveness or efficacy of many vaccines in immunocompromised hosts. However, in the last 10 years we have been starting get more data for some of the vaccines – for example, pneumococcal vaccine, influenza, shingles vaccine – but we still don’t have a lot of information on some of the very basic vaccines like meningococcal vaccine, DPT or Hemophilus vaccines.

Even for the vaccines where we do have data, I think a lot of the information we have is related to the vaccine immunogenicity – antibody responses and T-cell responses.  This means we are always trying to extrapolate effectiveness from immunogenicity to ascertain whether there is protection. It would be very nice to have direct data on efficacy and effectiveness in immunocompromised populations, and I would say that is one of the biggest gaps.

Have there been any recent updates in guidelines for vaccination of immunocompromised hosts?

There have been some guidelines that have been published recently. For example, the organ transplant vaccination guidelines, published by the American Society of Transplantation were updated in 2019. The Infectious Diseases Society of America vaccination guidelines for immunocompromised hosts were published in 2014. The Europeans have produced guidelines for stem cell patients, and those were just published in Lancet Infectious Diseases in 2019.

What is new in those guidelines? I think the American Society of Transplantation guidelines for vaccination of solid organ transplant recipients probably have the most changes. One of the changes is giving meningococcal B vaccines to organ transplant recipients that receive a complement inhibitor. Another one is expanding the age indication for HPV vaccine up to age 45 from the previous maximum age of 26 years.  Moreover, the inactivated shingles vaccine is now recommended for use in those that are over 50 years of age and can be considered for those that are less than 50. And then finally, for influenza vaccine there are more data on high-dose vaccine, and there is some preferential recommendation for the high-dose vaccine in this population.

Are there any other strategies apart from vaccination that could be used to prevent infection in immunocompromised hosts?

Some of our traditional strategies have been using preventative antibiotics. Although now with increasing resistance, I think those strategies are probably not going to be helpful and ideally should not be used. Another strategy would be to vaccinate the circle of care, so making sure that healthcare workers and close contacts who are with these patients are vaccinated. Then of course we have infection control measures, which we should all practice, such as good handwashing.

Do you think the immunocompromised population is growing with more transplants, more chemotherapy?

Definitely. Taking cancer as an example, cancer rates are increasing, and chemotherapy is being given to older individuals – ageism doesn’t exist anymore, it is basically how functionally well you are. In addition, we are using new anti-cancer treatments such as checkpoint inhibitors, and we need to figure out how they interact with vaccines. So, there is definitely a growing population there.

In the transplant setting, we are transplanting more than ever. For solid organ transplants, end-stage kidney disease, end-stage lung disease, and end-stage liver disease are increasing. For example, a huge reason for liver transplant is non-alcoholic steatohepatitis, which is correlated with obesity and the incidence of this is increasing. Finally, there are more biologics for inflammatory bowel disease or rheumatologic disease being used. So, because of a lot of epidemiologic factors and new treatments, we are definitely increasing our immunocompromised population.

Finally, is there anything else you would like to add about your research or your thoughts on the field?

I think we need to pay more attention to the growing population of immunocompromised with regards to vaccine recommendations. Traditionally, we have not had special vaccine recommendations for these groups. I think that for future vaccines, when vaccine advisory organizations like National Advisory Committee on Immunization, or the Advisory Committee on Immunization Practices, put out a recommendation for a vaccine, they should also put out a complementary recommendation for immunocompromised persons as well. I understand that adds a burden of work and there aren’t a lot of data sometimes to base that on, however, I think even simply stating that ‘there are no data, therefore, we would currently recommend that this vaccine be used the same way in immunocompromised as you would in the general population’ would be helpful.  Without specific guidance, providing these recommendations falls to societies or niche groups.

The other thing is the field of immunocompromised moves really fast in terms of new immunosuppressives, side-effects profiles of vaccines etc. and it can be hard to keep up. As I mentioned, it falls upon smaller groups to make guidelines and it would be nice to see those guidelines integrated on a broader scale. I think that is happening to a certain degree with the inactivated shingles vaccine – there are separate recommendations for immunocompetent and immunocompromised – so, it is starting to happen.

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