TLR7/8 Adjuvant Overcomes Newborn Hyporesponsiveness to Pneumococcal Conjugate Vaccine
The molecule 3M-052 offers effective immunization with one birth dose, representing a new paradigm in early life vaccine development
Technology Overview
Infection is the most common cause of mortality in early life, and immunization is the most promising biomedical intervention to reduce this burden. However, newborns and young infants fail to respond optimally to most vaccines, demonstrated by slow initiation, low immunogenicity, and reduced persistence of functional antibodies and cell-mediated responses. Adjuvantation enhances vaccine immunogenicity, but responses of human newborn leukocytes to most candidate adjuvants, including most TLR agonists, are functionally distinct.
The molecule 3M-052 is a locally acting lipidated imidazoquinoline TLR7/8 agonist adjuvant in mice, which can induce robust Th1 cytokine production by human newborn leukocytes in vitro, alone and in synergy with the alum-adjuvanted pneumococcal conjugate vaccine 13 (PCV13).
Further Details:
• Dowling DJ, van Haren SD, Scheid A, et al. TLR7/8 adjuvant overcomes newborn hyporesponsiveness to pneumococcal conjugate vaccine at birth. JCI Insight. 2017;2(6):e91020. Published 2017 Mar 23. doi:10.1172/jci.insight.91020
Stage of Development
Proof of concept:
• 3M-052, a locally acting TLR7/8 agonist, synergistically enhances type 1 immunity from newborn leukocytes when combined with pneumococcal conjugate vaccine in vitro (Figure 1).
• 3M-052 dramatically enhanced generation of Th1 neonatal CD4+ cells in vivo when administrated with PCV13 on the first day of life to rhesus macaques, along with activation of newborn and infant S. pneumoniae-specific B cells, serotype- specific antibody titers, and opsonophagocytic killing.
• Single dose at birth of PCV13 plus 0.1 mg/kg 3M-052 induced S. pneumoniae-specific IgG responses ~10–100 times greater than a single birth dose of PCV13 alone
• In vivo adjuvanticity of 3M-052 is dose dependent.
• Addition of a TLR7/8 agonist accelerates neonatal serotype-specific antibody responses to PCV13.
Benefits
• TLR7/8 agonist 3M-052 has a dose dependent adjuvanticity
• 3M-052 offers effective immunization with one birth dose, representing a new paradigm in early life vaccine development
Applications
- Vaccine adjuvants
- Immunomodulation
- Pneumococcal infection
Patents
- WO2018175854 A1: Methods and compositions relating to adjuvants
IP Status
