Well-defined and potent liposomal meningococcal B vaccines adjuvated with LPS derivatives.
Potent liposomal PorA formulations containing various lipopolysaccharide (LPS) derivatives were developed. The following adjuvants were compared: the commonly used aluminum phosphate (AlPO(4)), and three LPS like adjuvants: monophosphoryl lipid A (MPL), lipopolysaccharide (galE LPS) and the less toxic LPS mutant lpxL1. The immunogenicity in mice was evaluated and compared with that against an outer membrane vesicle (OMV) vaccine. The IgG isotype distribution and bactericidal activity were determined. Furthermore, PorA specific proliferation of lymph node cells after immunization and restimulation in vitro was studied with selected formulations. Both AlPO(4) and MPL were unable to improve the functional immunogenicity (i.e. bactericidal response) of liposomal PorA. Besides, when these adjuvants were used, the percentage of responders in the groups did not reach 100%. This was also observed with non adjuvated PorA-liposomes or OMV. Of the adjuvants studied, only galE LPS and lpxL1 LPS were capable of increasing the immunogenicity and avoid non responsiveness against PorA-liposomes. Importantly, the adjuvant activity of lpxL1 LPS was accompanied by an improved PorA specific proliferation of lymph node cells and a concomitant increase in IL-2 production. In conclusion and considering its lower toxicity, lpxL1 LPS adjuvated liposomes are superior to other formulations tested.
Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
Carmen
C
Arigita
Thomas
T
Luijkx
Wim
W
Jiskoot
Martien
M
Poelen
Wim E
WE
Hennink
Daan J A
DJ
Crommelin
Peter van der
Pv
Ley
Cecile van
Cv
Els
Gideon F A
GF
Kersten
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage; D001425:Bacterial Outer Membrane Proteins / Q000008:administration & dosage* / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D008081:Liposomes / Q000008:administration & dosage*; D008198:Lymph Nodes / Q000276:immunology; D008585:Meningitis, Meningococcal / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D051379:Mice; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D018272:Porins / Q000008:administration & dosage / Q000276:immunology
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D007376:Interleukin-2; D008070:Lipopolysaccharides; D008081:Liposomes; D022401:Meningococcal Vaccines; D018272:Porins; C057699:porin protein, Neisseria