TY - JOUR
T1 - Recombinant polymorphic membrane protein D in combination with a novel, second-generation lipid adjuvant protects against intra-vaginal Chlamydia trachomatis infection in mice
AU - Kaye, Paul
AU - Lacey, Charles John Nash
AU - Paes, William Neville Wayne
AU - Brzozowski, Andrzej Marek
AU - Bland, John Martin
AU - Brown, Najmeeyah
AU - Reed, Steve
AU - Carter, Darrick
AU - Cole, Rhea
PY - 2016/7/29
Y1 - 2016/7/29
N2 - The development of a chlamydial vaccine that elicits protective mucosal immunity is of paramount importance in combatting the global spread of sexually transmitted Chlamydia trachomatis (Ct) infections. While the identification and prioritization of chlamydial antigens is a crucial prerequisite for efficacious vaccine design, it is likely that novel adjuvant development and selection will also play a pivotal role in the translational potential of preclinical Ct vaccines. Although the molecular nature of the immuno-modulatory component is of primary importance, adjuvant formulation and delivery systems may also govern vaccine efficacy and potency. Our study provides the first preclinical evaluation of recombinant Ct polymorphic membrane protein D (rPmpD) in combination with three different formulations of a novel second-generation lipid adjuvant (SLA). SLA was rationally designed in silico by modification of glucopyranosyl lipid adjuvant (GLA), a TLR4 agonistic precursor molecule currently in Phase II clinical development. We demonstrate robust protection against intra-vaginal Ct challenge in mice, evidenced by significantly enhanced resistance to infection and reduction in mean bacterial load. Strikingly, protection was found to correlate with the presence of robust anti-rPmpD serum and cervico-vaginal IgG titres, even in the absence of adjuvant-induced Th1-type cellular immune responses elicited by each SLA formulation, and we further show that anti-rPmpD antibodies recognize Ct EBs. These findings highlight the utility of SLA and rational molecular design of adjuvants in preclinical Ct vaccine development, but also suggest an important role for anti-rPmpD antibodies in protection against urogenital Ct infection.
AB - The development of a chlamydial vaccine that elicits protective mucosal immunity is of paramount importance in combatting the global spread of sexually transmitted Chlamydia trachomatis (Ct) infections. While the identification and prioritization of chlamydial antigens is a crucial prerequisite for efficacious vaccine design, it is likely that novel adjuvant development and selection will also play a pivotal role in the translational potential of preclinical Ct vaccines. Although the molecular nature of the immuno-modulatory component is of primary importance, adjuvant formulation and delivery systems may also govern vaccine efficacy and potency. Our study provides the first preclinical evaluation of recombinant Ct polymorphic membrane protein D (rPmpD) in combination with three different formulations of a novel second-generation lipid adjuvant (SLA). SLA was rationally designed in silico by modification of glucopyranosyl lipid adjuvant (GLA), a TLR4 agonistic precursor molecule currently in Phase II clinical development. We demonstrate robust protection against intra-vaginal Ct challenge in mice, evidenced by significantly enhanced resistance to infection and reduction in mean bacterial load. Strikingly, protection was found to correlate with the presence of robust anti-rPmpD serum and cervico-vaginal IgG titres, even in the absence of adjuvant-induced Th1-type cellular immune responses elicited by each SLA formulation, and we further show that anti-rPmpD antibodies recognize Ct EBs. These findings highlight the utility of SLA and rational molecular design of adjuvants in preclinical Ct vaccine development, but also suggest an important role for anti-rPmpD antibodies in protection against urogenital Ct infection.
KW - Chlamydia trachomatis
KW - Pmps
KW - TLR4 adjuvant
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=84977139178&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2016.06.081
DO - 10.1016/j.vaccine.2016.06.081
M3 - Article
SN - 0264-410X
VL - 34
SP - 4123
EP - 4131
JO - Vaccine
JF - Vaccine
IS - 35
ER -