Rasmus Mortensen

Statens Serum Institut, Copenhagen, Denmark

A next-generation TB vaccine designed for induction of Th17 cells and synergy with BCG

Tuberculosis (TB) remains a leading cause of death from infectious diseases and the impact of the COVID-19 pandemic has increased both mortality and incidence. More effective vaccines are therefore needed subunit vaccines represent an attractive platform. However, the availability of potent adjuvants with distinct immune signatures is limited and despite accumulating evidence for a protective role of so-called Th17 cells, none of the existing adjuvants induces robust Th17 responses. To address this, we have developed a next-generation TB vaccine that is delivered in a novel liposomal adjuvant that induce potent Th1/Th17 responses in both mice and non-human primates. Consisting of eight Mtb-specific antigens, this vaccine also bypasses BCG-induced immune responses, which leads to further improvements in the Th17 response in comparison to ‘traditional’ BCG boosting vaccines. We will discuss the way to vaccine design, potential mechanisms of protection and plans for clinical testing in South Africa.

Selected references

• Aagaard C, Knudsen NPH, Sohn I, Izzo AA, Kim H, Kristiansen EH, Lindenstrøm T, Agger EM, Rasmussen M, Shin SJ, Rosenkrands I, Andersen P, Mortensen R. Immunization with Mycobacterium tuberculosis-Specific Antigens Bypasses T Cell Differentiation from Prior Bacillus Calmette-Guérin Vaccination and Improves Protection in Mice. J Immunol 2020 Oct 15;205(8):2146-2155
• Woodworth JS, Clemmensen HS, Battey H, Dijkman K, Lindenstrøm T, Laureano RS, Taplitz R, Morgan J, Aagaard C, Rosenkrands I, Lindestam Arlehamn CS, Andersen P, Mortensen R. A Mycobacterium tuberculosis-specific subunit vaccine that provides synergistic immunity upon co-administration with Bacillus Calmette- Guérin. Nat Commun 2021 Nov 18;12(1):6658
• Dijkman K, Lindenstrøm T, Rosenkrands I, Søe R, Woodworth JS, Lindestam Arlehamn CS, Mortensen R. A protective, single-visit TB vaccination regimen by co-administration of a subunit vaccine with BCG. NPJ Vaccines 2023 May 9;8(1):66
• Woodworth JS, Contreras V, Christensen D, Naninck T, Kahlaoui N, Gallouët AS, Langlois S, Burban E, Joly C, Gros W, Dereuddre-Bosquet N, Morin J, Olsen ML, Rosenkrands I, Stein AK, Wood GK, Follmann F, Lindenstrøm T, LeGrand R, Pedersen GK, Mortensen R. A novel adjuvant formulation induces robust Th1/Th17 memory and mucosal recall responses in Non-Human Primates. bioRxiv [Preprint]. 2023 Feb 23:2023.02.23.529651. doi: 10.1101/2023.02.23.529651

• https://classic.clinicaltrials.gov/ct2/show/NCT06050356