Deepak Kaushal, PhD, on Tuberculosis Vaccine Development

In this podcast, Deepak Kaushal, PhD, talks about his team's work on developing a new tuberculosis vaccine, what the vaccine would mean for the future of immunology, and more.

Additional Resource:

• Laddy DJ, Bonavia A, Hanekom WA, Kaushal D, et al. Toward tuberculosis vaccine development: recommendations for nonhuman primate study design. Infect Immun. 2018;86(2). https://doi.org/10.1128/iai.00776-17 

Deepak Kaushal, PhD, is a professor at Texas Biomedical Research Institute and the director of the Southwest National Primate Research Center, which is one of the 7 nationally funded primate research centers in the United States, at Texas Biomedical Research Institute in San Antonio, Texas.

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TRANSCRIPT:

Amanda Balbi: Hello everyone, and welcome to another installment of Podcasts360, your go-to resource for medical news and clinical updates. I’m your moderator, Amanda Balbi with Consultant360 Specialty Network.

August is National Immunization Awareness Month, which is a time to highlight the importance of vaccination for people of all ages. With us today to discuss his team’s work on developing a new tuberculosis vaccine is Dr Deepak Kaushal, who is a professor at Texas Biomedical Research Institute and the director of the Southwest National Primate Research Center, which is one of the 7 nationally funded primate research centers in the United States, at Texas Biomedical Research Institute in San Antonio, Texas.

Thank you so much for joining me today, Dr Kaushal.

Deepak Kaushal: Wonderful, thank you.

Amanda Balbi: I know your group has worked on tuberculosis-HIV vaccine candidates in the past. Are you currently investigating any new candidate vaccines?

Deepak Kaushal: Yes, my lab is funded to study the further development of the TB vaccine. We published this work, many years ago now. We work with TB vaccines that are actually derived from TB.

So, there are several concepts in TB vaccination. TB, as you know, like HIV and like malaria has proven to be not readily vaccinable. So development of a vaccine to prevent TB has not been an easy time.

There are several concepts. Some people work with what are known as [indecipherable 1:45], which are one or more protein components derived from TB. Others work with DNA vaccines. One of the most popular and recently depopularized format is BCG, which is a distant cousin of Mycobacterium known as Mycobacterium bovis, which is a cattle TB bacterium.

BCG is designed from making mutations in that particular strain. So it’s safe. It doesn't cause disease in normal human beings.

And then the fourth concept is—we looked at, traditionally, a hundred years’ of data that's available with BCG, and we realized that BCG is very safe. However, it doesn't cause [indecipherable 2:28] the same kind of immune system that TB does. And some of those immune responses are really important for the immune system to have [indecipherable 2:36].

So we've taken the approach of taking TB and then rationally reducing its pathogenicity, while retaining ability to cause immune responses.

People have taken the approach of making BCG better, and we've taken the approach of reducing the virulence of TB. We are not the only ones; there are several other groups.

So we have one candidate vaccine that we've shown is safe in monkeys and can protect immunogenicity. We've since done several other experiments and we've shown that particular strain is not just safe in one species of monkey but also in another. It's not an effect that specific to that particular. It's not a narrow effect.

And these are unpublished data by the way. We've gone ahead and shown that our vaccine works not only against one particular strain of TB, but also other signs of TB. So, it's not a homologous effect; it’s an analogous effect as well. So that vaccine is the real deal.

However, according to Geneva Convention for development of rational TB vaccines, it is required that a candidate must have more than one gene that must be mutated. Our vaccine currently has [indecipherable 3:47] one particular gene that is missing.

And so it sounds easier—just introduce another mutation and some other gene—but what we have to do is introduce other mutations to retain the original mutation, and then retain the immunogenicity and the protective effect that we are getting.

And many of these [indecipherable 4:08] bacteria are interrelated and sometimes you just tinker with one particular genetic part of the genome. And then it has undesired effects otherwise. So what we've been doing is we’ve taken the mutant bacteria that we have—the vaccine that we have—and we are trying to make it more safe by introducing other mutations and then testing these things in the monkey model that we have.

So we do hope in the next 2 or 3 years, these are painfully laborious processes. The Tb model in particular is really slow. It's very expensive. And if we had more support, we can work quicker. But right now with the level of support that we have from the National Institutes of Health, we are making progress slowly in developing a vaccine that could retain the protective effect in monkeys and would be safe enough that one could argue that it should be tried out in human beings.

Amanda Balbi: Great! Thank you so much, and we look forward to reading that published data.

Deepak Kaushal: Thank you. It was a pleasure.