Vaccine Adjuvant Systems containing monophosphoryl lipid A and QS21 induce strong and persistent hum

[Guest guest]

Vaccine. 2008 Jan 14 [Epub ahead of print]

Vaccine Adjuvant Systems containing monophosphoryl lipid A and QS21 induce

strong and persistent humoral and T cell responses against hepatitis B surface

antigen in healthy adult volunteers.

Vandepapelière P, Horsmans Y, Moris P, Van Mechelen M, Janssens M, Koutsoukos M,

Van Belle P, Clement F, Hanon E, Wettendorff M, Garçon N, Leroux-Roels G.

GlaxoKline Biologicals, 89 rue de l’Institut, 1330 Rixensart, Belgium.

A randomised, double-blind study assessing the potential of four adjuvants in

combination with recombinant hepatitis B surface antigen has been conducted to

evaluate humoral and cell-mediated immune responses in healthy adults after

three vaccine doses at months 0, 1 and 10. Three Adjuvant Systems (AS) contained

3-O-desacyl-4'-monophosphoryl lipid A (MPL) and QS21, formulated either with an

oil-in-water emulsion (AS02B and AS02V) or with liposomes (AS01B). The fourth

adjuvant was CpG oligonucleotide. High levels of antibodies were induced by all

adjuvants, whereas cell-mediated immune responses, including cytolytic T cells

and strong and persistent CD4(+) T cell response were mainly observed with the

three MPL/QS21-containing Adjuvant Systems. The CD4(+) T cell response was

characterised in vitro by vigorous lymphoproliferation, high IFN-gamma and

moderate IL-5 production. Antigen-specific T cell immune response was further

confirmed ex vivo by detection of IL-2- and IFN-gamma-producing CD4(+) T cells,

and in vivo by measuring increased levels of IFN-gamma in the serum and

delayed-type hypersensitivity (DTH) responses. The CpG adjuvanted vaccine

induced consistently lower immune responses for all parameters. All vaccine

adjuvants were shown to be safe with acceptable reactogenicity profiles. The

majority of subjects reported local reactions at the injection site after

vaccination while general reactions were recorded less frequently. No

vaccine-related serious adverse event was reported. Importantly, no increase in

markers of auto-immunity and allergy was detected over the whole study course.

In conclusion, the Adjuvant Systems containing MPL/QS21, in combination with

hepatitis B surface antigen, induced very strong humoral and cellular immune

responses in healthy adults. The AS01B-adjuvanted vaccine induced the strongest

and most durable specific cellular immune responses after two doses. These

Adjuvant Systems, when added to recombinant protein antigens, can be fundamental

to develop effective prophylactic vaccines against complex pathogens, e.g.

malaria, HIV infection and tuberculosis, and for special target populations such

as subjects with an impaired immune response, due to age or medical conditions.

PMID: 18272264 [PubMed - as supplied by publisher]

_________________________________________________________________

Climb to the top of the charts! Play the word scramble challenge with star

power.

http://club.live.com/star_shuffle.aspx?icid=starshuffle_wlmailtextlink_jan

[Guest guest]

Vaccine. 2008 Jan 14 [Epub ahead of print]

Vaccine Adjuvant Systems containing monophosphoryl lipid A and QS21 induce

strong and persistent humoral and T cell responses against hepatitis B surface

antigen in healthy adult volunteers.

Vandepapelière P, Horsmans Y, Moris P, Van Mechelen M, Janssens M, Koutsoukos M,

Van Belle P, Clement F, Hanon E, Wettendorff M, Garçon N, Leroux-Roels G.

GlaxoKline Biologicals, 89 rue de l’Institut, 1330 Rixensart, Belgium.

A randomised, double-blind study assessing the potential of four adjuvants in

combination with recombinant hepatitis B surface antigen has been conducted to

evaluate humoral and cell-mediated immune responses in healthy adults after

three vaccine doses at months 0, 1 and 10. Three Adjuvant Systems (AS) contained

3-O-desacyl-4'-monophosphoryl lipid A (MPL) and QS21, formulated either with an

oil-in-water emulsion (AS02B and AS02V) or with liposomes (AS01B). The fourth

adjuvant was CpG oligonucleotide. High levels of antibodies were induced by all

adjuvants, whereas cell-mediated immune responses, including cytolytic T cells

and strong and persistent CD4(+) T cell response were mainly observed with the

three MPL/QS21-containing Adjuvant Systems. The CD4(+) T cell response was

characterised in vitro by vigorous lymphoproliferation, high IFN-gamma and

moderate IL-5 production. Antigen-specific T cell immune response was further

confirmed ex vivo by detection of IL-2- and IFN-gamma-producing CD4(+) T cells,

and in vivo by measuring increased levels of IFN-gamma in the serum and

delayed-type hypersensitivity (DTH) responses. The CpG adjuvanted vaccine

induced consistently lower immune responses for all parameters. All vaccine

adjuvants were shown to be safe with acceptable reactogenicity profiles. The

majority of subjects reported local reactions at the injection site after

vaccination while general reactions were recorded less frequently. No

vaccine-related serious adverse event was reported. Importantly, no increase in

markers of auto-immunity and allergy was detected over the whole study course.

In conclusion, the Adjuvant Systems containing MPL/QS21, in combination with

hepatitis B surface antigen, induced very strong humoral and cellular immune

responses in healthy adults. The AS01B-adjuvanted vaccine induced the strongest

and most durable specific cellular immune responses after two doses. These

Adjuvant Systems, when added to recombinant protein antigens, can be fundamental

to develop effective prophylactic vaccines against complex pathogens, e.g.

malaria, HIV infection and tuberculosis, and for special target populations such

as subjects with an impaired immune response, due to age or medical conditions.

PMID: 18272264 [PubMed - as supplied by publisher]

_________________________________________________________________

Climb to the top of the charts! Play the word scramble challenge with star

power.

http://club.live.com/star_shuffle.aspx?icid=starshuffle_wlmailtextlink_jan