The disease tuberculosis (TB) has been with us since around 10,000 years ago, when we humans began living in communities. We in India have known it since ancient times, just as the people in Western Asia have. Sanskrit texts dating back to 1500 BCE knew it and called it Sosha . Sushruta Samhita (ca. 600 BC) recommended that the disease be treated with breast milk, alcohol and rest. The compendium called Madhukosa (ca. 900 AD) described the disease as Yaksma or consumption .That the disease is transmitted from to person (even animals to humans) through sputum and cough was also known. Various medications were tried with little success. It was in 1882 that the German microbiologist H.H. Robert Koch discovered that the disease is caused by a germ he called Mycobacterium tuberculosis (or Mtb) for which he was awarded the Nobel Prize in 1905. He also attempted to find drugs to treat TB and came out with a product he called tuberculin, though with little success. Since then, drugs against TB have been successfully marketed, e.g., Rifampicin, Isoniazid, Pyrazinamide and the latest ones Pretomanid and Bedaquiline. The Indian government is using most or all of them to treat millions of TB cases every year.
Prevention is better than cure. The field immunology attempts to practice this proverb and tries to stop the invading germs from entering the body and causing disease. Success in producing such a product which can provide immunity against TB came about through the work of two French bacteriologists, Albert Calmette and Camile Guerin during 1908-1921. They came out with the product called Bacillus Calmette-Guerin or BCG. When BCG was injected in the human’s body as a vaccine, it provided immunity against the attack of Mtb. The first TB vaccine was thus born and is being used across the world even today on infants (and children below 15), affording them protection against TB. Remarkably, the protection lasts for as long as 20 years, as recent studies have shown. India has been using BCG vaccine with success for decades now.
Breathe in the vaccine
However, it has come to be known that while BCG is good for children, it may not be as effective in adults, who get TB of the lungs (pulmonary) more often, as opposed to in the intestines, bones or the urinary tract. It is also not effective if a person is affected by other diseases (for example, AIDS) and thus immune-compromised. Also, occasionally people react to BCG with some fever and also skin itching at the injection spot, making it uncomfortable to use. There is thus the need for alternative vaccines, which can work by themselves and also act as boosters for BCG. It will also help if these new vaccines are easier delivered in other modes, rather than by injection.
An exciting way to deliver vaccines was initiated almost 50 years ago and involved inhaling it through the nose into the lungs or the pulmonary route of vaccination. It was first tried in England in 1951 on a flock of chicken through aerosol vaccination against a virus. It was later tried with BCG in 1968, in guinea pigs and a few humans. In Mexico, they succeeded in immunising school-children against measles during 1988-1990, and later by others on TB (see review by Contreras, Awasthi, Hanif and Hickey: Inhaled vaccines for the prevention of TB 2012; Mycobacterial Disease S1:002. doi: 10.4172/2161-1068 S1-002). It is also worth noting that using this route needs no needles, does not need clinically trained persons, cuts down waste and is lower in cost.
When the pathogenic organism invades the body, it uses a molecule to pierce through and, using the material therein, to multiply and cause havoc. The host (scientists are polite!) body in turn fights back by using its immunity apparatus. The so-called B Cells there synthesise proteins called antibodies which bind with the invader and disable it. Plus, the host stores this mechanism for future, in case the pathogen attacks at a later time. This is the basis behind vaccination, which is good for years.
Actually, the whole germ is not needed for antibody generation. Even a part of the molecule (the “business region” or the epitope) suffices for the generation of antibodies by the B Cells. The immune apparatus has another class, called T cells which work in tandem with B cells. Molecules in T cells help “kill” the invaders. Here again, we do not need the whole molecule, but that part which helps in the process, as “adjuvants” for immune response.
A group at the University of Sydney in Australia has been creatively using these three principles to generate an inhalable vaccine against TB. Their publication appears in the latest issue of Journal of Medicinal Chemistry (Ashhurst. A, et al., J Med Chem. 2019 Aug 16. doi: 10.1021/acs.jmedchem.9b00832.). They chemically synthesised a part of the molecules of T cells as adjuvants on one hand and linked it chemically with the epitope part of Mtb (which too they synthesised in the lab). The so-synthesised product (call it compound I) was then administered through the nose of mice. The mice were then infected with Mtb and, after a few weeks the lungs and spleens of the infected mice tested. The bacterial load was found to be substantially low proving that aerosol administration of I was protective as a vaccine candidate. Also, the inhalation route of administering the vaccine candidate was seen to be better than the injection route. This should make children and nervous adults happy!
dbala@lvpei.org
