Nasal DNA Vaccine Protects Against Tuberculosis

Researchers at Johns Hopkins Medicine and the Johns Hopkins Bloomberg School of Public Health have developed an experimental therapeutic nasal DNA vaccine for tuberculosis (TB). The vaccine is designed to help the immune system identify and attack drug-tolerant TB bacteria known as “persisters,” which can survive lengthy antibiotic treatment and later trigger a relapse of the disease.

According to Styliani Karanika, MD, a faculty member of the Johns Hopkins Center for Tuberculosis Research and assistant professor of medicine at the Johns Hopkins University School of Medicine, the vaccine combines two genes, relMtb and Mip3α, and is administered through the nose to take advantage of several biological mechanisms that may strengthen immunity against TB.

“First, TB bacteria possess a gene, relMtb, that produces a protein, RelMtb, to help the microbes survive hostile conditions such as antibiotic exposure, low oxygen and nutrient limitation by entering a drug-tolerant persistent state,” says Dr. Karanika. “Fusing relMtb with the Mip3α gene produces a signal that attracts immature dendritic cells — key cells that pick up TB proteins and ‘present’ them to T cells, the immune cells that help coordinate a targeted attack on the TB bacteria.”

The vaccine is also designed to focus immune activity where TB infections begin.

“Finally, intranasal delivery focuses vaccination on the respiratory mucosa in the lungs where TB infection occurs, helping generate long-lasting localized T-cell immunity in the airways and lungs, along with systemic immune responses,” says Dr. Karanika.

By combining these mechanisms, the researchers sought to strengthen immune defenses directly within the respiratory tract. In mouse experiments, the vaccine increased recruitment and activation of dendritic cells, improved the organization of dendritic cells and T cells within lung tissue, and generated durable, antigen-stimulated T-cell responses — both locally and systemically — from CD4 (also known as helper T cells) and CD8 (also known as killer T-cells).

The team also evaluated the vaccine in rhesus macaques and found it generated measurable TB-specific immune responses in both the bloodstream and airways. These responses resembled those associated with reduced bacterial levels in the lungs of vaccinated mice.

Researchers observed that the immune responses lasted for at least six months, suggesting the vaccine may provide durable protection. However, Dr. Karanika notes that the primate study assessed immune activation only and did not test how the animals responded to an actual TB infection. She says additional research will be required before the vaccine can advance to human clinical trials.