Bordetella pertussis monophosphoryl lipid A as adjuvant for inactivated split virion influenza vaccine in mice.
The world production capacity of influenza vaccines is a concern in face of the potential influenza pandemic. The use of adjuvants could increase several fold the current installed production capacity. Bordetella pertussis monophosphyl lipid A (MPLA) was produced by acid hydrolysis of LPS, obtained as a by-product of its removal from cellular pertussis vaccine, generating a product with 4 side chains. We have investigated different formulations including MPLA alone or combined with Al(OH)(3) as adjuvants for an inactivated split virion influenza vaccine. Our results demonstrate that MPLA at concentrations as low as 0.01 microg per dose of vaccine is effective, even with a 4-fold reduction of the regular vaccine dose, as measured by the induction of protective hemagglutination inhibition (HAI) titers. Al(OH)(3) can be combined with 0.01-10 microg MPLA, inducing even higher immune responses. Al(OH)(3) caused a drift of the immune response induced by the vaccine towards a Th2 profile, as evaluated by an increase in the IgG1:IgG2a ratio, while MPLA showed a more balanced response. Moreover, the use of MPLA and Al(OH)(3) combination led to the induction of the highest IgG levels together with the secretion of both IFN-gamma and IL-4. Although cell-mediated immune responses have not been usually taken into account for influenza vaccine formulations, they may be relevant for the induction of cross-protection as well as immunological memory for both inter-pandemic and pandemic influenza vaccines. Our results indicate that a more favorable profile of both humoral and cell-mediated immune responses may be obtained using the MPLA/Al(OH)(3) formulation.
Quintilio
Wagner
W
BioIndustrial Division, Instituto Butantan, São Paulo, SP, Brazil.
Kubrusly
Flavia S
FS
Iourtov
Dmitri
D
Miyaki
Cosue
C
Sakauchi
Maria Aparecida
MA
Lúcio
Fernanda
F
Dias
Sandra de Cássia
Sde C
Takata
Celia S
CS
Miyaji
Eliane N
EN
Higashi
Hisako G
HG
Leite
Luciana C C
LC
Raw
Isaias
I
D000276:Adjuvants, Immunologic / Q000302:isolation & purification / Q000494:pharmacology*; D000536:Aluminum Hydroxide / Q000494:pharmacology; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001886:Bordetella pertussis / Q000737:chemistry*; D006385:Hemagglutination Inhibition Tests; D007074:Immunoglobulin G / Q000097:blood; D007252:Influenza Vaccines / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008050:Lipid A / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D022223:Vaccines, Subunit / Q000276:immunology
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D008050:Lipid A; D022223:Vaccines, Subunit; D015847:Interleukin-4; D000536:Aluminum Hydroxide; D007371:Interferon-gamma; C048436:monophosphoryl lipid A