Designing Adjuvant Formulations to Promote Immunogenicity and Protective Efficacy of Leptospira Immunoglobulin-Like Protein A Subunit Vaccine

The leptospirosis burden on humans, especially in high-risk occupational groups and livestock, leads to public health and economic problems. Leptospirosis subunit vaccines have been under development and require further improvement to provide complete protection. Adjuvants can be used to enhance the amplitude, quality, and durability of immune responses. Previously, we demonstrated that LMQ adjuvant (neutral liposomes containing monophosphoryl lipid A (MPL) and Quillaja saponaria derived QS21 saponin) promoted protective efficacy of LigAc vaccine against Leptospira challenge. To promote immunogenicity and protective efficacy of the subunit vaccines, three alternative adjuvants based on neutral liposomes or squalene-in-water emulsion were evaluated in this study. LQ and LQuil adjuvants combined the neutral liposomes with the QS21 saponin or Quillaja saponaria derived QuilA(®) saponin, respectively. SQuil adjuvant combined a squalene-in-water emulsion with the QuilA(®) saponin. The immunogenicity and protective efficacy of LigAc (20 µg) formulated with the candidate adjuvants were conducted in golden Syrian hamsters. Hamsters were vaccinated three times at a 2-week interval, followed by a homologous challenge of L. interrogans serovar Pomona. The results showed that LigAc combined with LQ, LQuil, or SQuil adjuvants conferred substantial antibody responses and protective efficacy (survival rate, pathological change, and Leptospira renal colonization) comparable to LMQ adjuvant. The LigAc+LQ formulation conferred 62.5% survival but was not significantly different from LigAc+LMQ, LigAc+LQuil, and LigAc+SQuil formulations (50% survival). This study highlights the potential of saponin-containing adjuvants LMQ, LQ, LQuil, and SQuil for both human and animal leptospirosis vaccines.