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Infection and Immunity, October 2000, p. 5764-5770, Vol. 68, No. 10
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Carbohydrate Biopolymers Enhance Antibody Responses to Mucosally Delivered Vaccine Antigens

A. Bacon,1 J. Makin,2 P. J. Sizer,2 I. Jabbal-Gill,3 M. Hinchcliffe,3 L. Illum,3 S. Chatfield,1 and M. Roberts4,*

Vaccine Research Unit (Medeva Group Development), Department of Biochemistry, Imperial College of Science and Technology, London SW7 2AY,1 Medeva Group Development, Evans Medical Ltd., Speke, Liverpool L24 9GR,2 Danbiosyst, Albert Einstein Building, Highfields Science Park, Nottingham NG7 2TN,3 and Department of Veterinary Pathology, University of Glasgow Veterinary School, Glasgow G61 1QH,4 United Kingdom

Received 21 March 2000/Returned for modification 15 May 2000/Accepted 28 June 2000

We have evaluated the ability of two carbohydrate biopolymers, chitosan and gellan, to enhance antibody responses to subunit influenza virus vaccines delivered to the respiratory tracts of mice. Groups of mice were vaccinated three times intranasally (i.n.) with 10 µg of purified influenza B/Panama virus surface antigens (PSAs), which consist of hemagglutinin (HA) and neuraminidase (NA), either alone or admixed with chitosan or gellan solutions. Separate groups were vaccinated subcutaneously (s.c.) with PSAs adsorbed to Alhydrogel or chitosan or gellan alone i.n. Serum antibody responses were determined by enzyme-linked immunosorbent assay (ELISA) for influenza virus-specific immunoglobulin G (IgG) and by HA inhibition (HAI) and NA inhibition (NAI) assays. The local respiratory immune response was measured by assaying for influenza virus-specific IgA antibody in nasal secretions and by enumerating nasal and pulmonary lymphocytes secreting IgA, IgG, and IgM anti-influenza virus-specific antibodies by enzyme-linked immunospotting (ELISPOT). When administered alone i.n., B/Panama PSA was poorly immunogenic. Parenteral immunization with B/Panama PSA with Alhydrogel elicited high titers of anti-B/Panama antibodies in serum but a very poor respiratory anti-B/Panama IgA response. In contrast, i.n. immunization with PSA plus chitosan stimulated very strong local and systemic anti-B/Panama responses. Gellan also enhanced the local and serum antibody responses to i.n. PSA but not to the same extent as chitosan. The ability of chitosan to augment the immunogenicity of influenza vaccines given i.n. was confirmed using PSA prepared from an influenza A virus (A/Texas H1N1).

* Corresponding author. Mailing address: Department of Veterinary Pathology, Glasgow University Veterinary School, Bearsden Rd., Glasgow G61 1QH, United Kingdom. Phone: 0141 330 5780. Fax: 0141 330 5602. E-mail: M.Roberts{at}vet.gla.ac.uk.

Infection and Immunity, October 2000, p. 5764-5770, Vol. 68, No. 10
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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