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Infect Immun, June 1998, p. 2859-2865, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Liposomes Containing Lipid A Serve as an Adjuvant for Induction of Antibody and Cytotoxic T-Cell Responses against RTS,S Malaria Antigen

Roberta L. Richards,1,* Mangala Rao,1 Nabila M. Wassef,1 Gregory M. Glenn,1 Stephen W. Rothwell,2 and Carl R. Alving1

Departments of Membrane Biochemistry1 and Hematology and Vascular Biology,2 Walter Reed Army Institute of Research, Washington, D.C. 20307-5100

Received 30 December 1997/Returned for modification 11 February 1998/Accepted 24 March 1998

Encapsulation of soluble protein antigens in liposomes was previously shown to result in processing of antigen via the major histocompatibility complex class I pathway, as evidenced by costaining of the trans-Golgi region of murine bone marrow-derived macrophages (BMs) by fluorophore-labeled liposomal antigen and by a trans-Golgi-specific fluorescent lipid. Evidence is presented here that free or liposome-encapsulated RTS,S, a particulate malaria antigen consisting of hepatitis B particles coexpressed with epitopes from the Plasmodium falciparum circumsporozoite protein, also was localized in the trans-Golgi after incubation with BMs, suggesting processing by the class I pathway. An in vivo cytotoxic T-lymphocyte (CTL) response was detected, however, only after immunization with RTS,S encapsulated in liposomes containing lipid A and not after immunization with free RTS,S or with RTS,S encapsulated in liposomes lacking lipid A. Therefore, intracellular delivery of antigen containing CTL epitopes to the Golgi of BMs does not necessarily result in a CTL response in vivo unless an additional adjuvant, such as liposomes containing lipid A, is utilized. Encapsulation of RTS,S in liposomes containing monophosphoryl lipid A (MPL) resulted in a dose-dependent enhancement of the NANP-specific immunoglobulin G (IgG) antibody response compared to that of free RTS,S. The IgG1 and IgG2a subclasses predominated after immunization with RTS,S encapsulated in liposomes containing MPL. These results demonstrate that encapsulation of a lipid-containing particulate antigen, such as RTS,S, in liposomes containing lipid A can enhance both humoral and cellular immune responses.

* Corresponding author. Mailing address: Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC 20307-5100. Phone: (202) 782-3940. Fax: (202) 782-0721. E-mail: dr._roberta_owens{at}wrsmtp-ccmail.army.mil.

Infect Immun, June 1998, p. 2859-2865, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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