Treatment of Respiratory Infections

Each year, there are over four million deaths from respiratory infections worldwide. The impact in the developing world is severe and notably in the US, viral respiratory infections cost a total of $25 billion per annum. Particularly at risk are young children, the elderly, and sufferers of chronic conditions affecting the lungs, such as asthma, cystic fibrosis, lung cancer and chronic obstructive pulmonary disease (COPD). Some of these conditions are very common: asthma prevalence is at 7.4% in adults and 8.6% in children in the US1 and costs around 56 billion per year2, while COPD affects at least 11.5% of people over 653.

Respiratory tract infections that pose no risk for the general population can result in hospitalisation for patients with chronic lung conditions and viral respiratory tract infections are associated with 80-85% of asthma exacerbations. Similarly, the progression of COPD is accelerated by viral infections. Sufferers of these conditions are also highly susceptible to serious secondary bacterial infections such as pneumonia.

The absence of effective vaccines against viral respiratory infections and the emergence of multiple drug resistant bacteria that cause secondary infections have resulted in an unmet medical need for the prevention and treatment of respiratory infections, especially  for asthma and COPD patients.

To both prevent and treat viral lung infections and secondary bacterial infections, Innavac is developing novel synthetic TLR2 agonists which activate the innate immune system, the first line of defence in the respiratory tract.

Through their surface and endogenous TLRs, immune cells of the respiratory tract detect and become activated in response to the detection of highly-conserved microbial structures from pathogenic bacteria and viruses. This recognition is instrumental in initiating immune responses to both bacteria and viruses which will lead to their elimination. Importantly, there is evidence that TLR2 plays a critical role in priming immune cells for increased Type I IFN production in response to subsequent TLR signaling. By directly binding to the surface TLR2, Innavac’s TLR2 agonists stimulate the innate immune system in an antigen-independent manner, making identification of the invading pathogen unnecessary. Thanks to this unique mechanism of action, TLR2 agonists have the potential to act as broad-spectrum prophylactic and therapeutic agents.

Pre-clinical in vivo proof-of-concept data has demonstrated the effectiveness of TLR2 agonists in a number of disease models, including the influenza H1N1 challenge, a bacterial-mediated lung infection model and the Streptococcus pneumonia/influenza co-infection model4,5.

Innavac’s new antigen-independent approach has the potential to prevent and treat a range of lung infections which are not only extremely burdensome for the general population but can prove life-threatening to vulnerable populations.

 

References

  1. United States Centers for Disease Control and Prevention.
  2. United States Environmental Protection Agency.
  3. United States Centers for Disease Control and Prevention.
  4. Tan et al. 2012. Intranasal Administration of the TLR2 Agonist Pam2Cys Provides Rapid Protection against Influenza in Mice. Mol. Pharmaceutics 2012, 9, 2710−2718.
  5. Mifsud et al. 2016. Reducing the impact of influenza-associated secondary pneumococcal infections. Immunology and Cell Biology (2016) 94, 101–108.