Barrier | Potential solution(s) |
Understanding how immunity develops • Poor immunogenicity and/or durability • Lack of correlates of protection • Inefficient activation of innate immunity • Lack of animal models with predictive value |
Systems biology studies Identify non-humoral correlates of protection Better understanding of the effector functions associated with spontaneous resolution of infection Vaccines inducing cellular immunity Laboratory assays measuring functional responses correlated with clinical protection |
Host variability • Inter-individual variability in vaccine response • Non-responder populations • Sex, age, race, ethnic differences in response |
Age, sex, or population-based vaccine formulations Diagnostic tests to predict vaccine response |
Pathogen variability • Pathogen diversity • Antigenic drift and antigenic shift • Hypervariable viruses • Complex biology (e.g., Plasmodium) • Active vs. latent vs. chronic infection • Host pathogen interactions • Immune response evasion mutants |
Vaccines eliciting broadly neutralizing Abs Multi-valent vaccines eliciting high affinity Ab to multiple serotypes Universal vaccine based on genetically conserved epitopes Vaccines targeting pre-erythrocytic, blood, and/or mosquito stages Interventions that mitigate pathogen immunomodulation during immune response to vaccination DNA vaccine targeting T cell responses to the partially conserved NS3 and C genes and Ab responses to the E protein |
Vaccine safety • Adverse events • Autoimmunity • Vaccine hesitancy |
Subunit, protein, and peptide-based vaccines incorporating novel adjuvants driving immunogenicity and durable protection Dose-sparing approaches |
Environmental and geographic factors • Poor nutrition/obesity • Co-infection • Prior immunity • Pollution |
DENV-vaccines for naïve and DENV-exposed individuals Vitamin supplementation coadministered with vaccination |