On 18th July 1981, in the suburbs of Paris, a pregnant woman died in a hospital after giving birth. The cause of death: Tuberculosis(TB). Will her kid also be a victim of this deadly disease? Fortunately along with kid, in the same place at the same time was born BCG- the first vaccine for Tuberculosis. The kid was vaccinated and led a TB free life.
Flash forward to 21st century and BCG still remains the sole vaccine for TB. But not everyone vaccinated is as lucky as that kid. The efficiency of the vaccine is not 100%. Needless to say, the hunt for a more effective vaccine is still on.
In a new study published in the Journal of Clinical Vaccine Immunology, scientists have identified a new candidate for the development of a more effective TB vaccine. “Rv1860, was found to stimulate CD8-positive (CD8+) T cells, a subset that strongly correlates with the protective immunity in several human and primate studies”, says Prof. Vijaya Satchidanandam of IISc and the lead author of the study.
What is this Rv1860? And what makes it a good candidate for an effective TB vaccine?
Lets start with a short background on vaccines. A vaccine is an agent – a dead or weakened pathogen, or a component of pathogen: protein, toxins etc, which stimulate the immune response in the host. So the next time when the actual pathogen attacks, the host responds with an increased immune response as it now ‘knows’ and ‘remembers’ the pathogen. Now, how do you describe a ‘good vaccine’? Better immune response, you might think. And, that’s absolutely right. Next obvious question, how do you measure an immune response? You might be surprised to know that scientists have not narrowed down even one reliable correlate of protective immune response against TB yet.
CD8+ T cells – a subset of T cells, which are a type of white blood cells, are increasingly being recognized for their active role in TB protection. And, our new candidate: Rv1860, stimulates just that! Rv1860 is a protein secreted byMycobacterium tuberculosis. It isthe deadly pathogen that causes tuberculosis – but not always!
Confused? Lets disentangle this.
An infection with Mycobacterium tuberculosis does not equate to active Tuberculosis disease. In most cases, the bacterium just hangs around in the body in a dormant state. Such people are said to have latent TB. Lets call them Group 1. In fact, the life-time probability of Group I to get active TB disease is only 10%. They usually lead a normal, healthy life. But some people with a poor immune response get infected and proceed to active TB earlier than others. Lets call this Group II.
What makes the immune response of Group I different from Group II? What if we can trigger the same response in Group II as in Group I and prevent them from getting active disease? This approach may be useful in constructing new and better TB vaccines.
For this study, the researchers recruited 30 healthy latently infected TB volunteers (Group I) and 20 TB patients with active disease (Group II). They treated blood samples of both groups with various peptides derived from our candidate-Rv1860. These peptides represent small parts of the protein Rv1860.
To measure the immune response, the researchers measured proliferation of Peripheral Blood Mononuclear Cells (PBMC). All the white blood cells (including T cells) come under PBMC. These are important components of human immune response. In both the groups, the researchers observed high PBMC proliferation. They further observed a significant production of one or more cytokines: IFN-g, TNF-a, IL-10 or IL-6 in response to one or more peptides. These cytokines are chemicals through which immune cells coordinate with each other while fighting a pathogen. The researchers further queried the contribution of T cells to the secretion of cytokines. They found that CD8+ T cells predominately secreted the cytokines IL-2 and IFN-g; although CD4+ T cells were also activated by the peptides. And, these responses were significantly greater in Group I – the healthy latently infected individuals than Group 2.
“This study was done on human subjects who were not HIV-positive– the most natural disease setting and hence the positive results are highly encouraging”, emphasizes Prof. Vijaya Satchidanandam.
Wouldn’t it be great if the new vaccine with Rv1860 could elicit the same immune response in vaccinated people that would halt TB infection in the latent stage?
Well, vaccine making is not a fast process. The researchers immediate next step is to validate the results with a larger human cohort next.
About the authors
Dr. Vijaya Satchidanandam: the lead author, is a Professor at Indian Institute of Science(IISc), Bangalore.
Naveen Kumar, Sunetra Biswas, Rajiv S. Jumani are graduate students at IISc. Chandni Jain, also from IISc, is a Project Assistant.
Dr. Rajni Rani is a Senior Staff Scientist at the National Institute of Immunology(NII), Delhi.
Bharti Aggarwal and Jaya Singh are project assistants at NII.
Dr. Mohan Rao Kotnur is a Chest Physician at M.S. Ramiah hospital, Bangalore
Dr. Anand Sridharan is a microbiologist at National Tuberculosis Institute,
Vijaya Satchidanandam: firstname.lastname@example.org
About the paper
Title: The secreted protein Rv1860 of Mycobacterium tuberculosis stimulates human polyfunctional CD8+ T cells.
Publication: Clinical and Vaccine Immunology Journal