CD71 targeting boosts immunogenicity of sublingually delivered influenza haemagglutinin antigen and protects against viral challenge in mice.
The delivery of vaccines to the sublingual mucosa is an attractive prospect due to the ease and acceptability of such an approach. However, novel adjuvant and delivery approaches are required to optimally vaccinate at this site. We have previously shown that conjugation of protein antigen to the iron transport molecule, transferrin, can significantly enhance mucosal immune responses. We tested whether conjugating influenza haemagglutinin to transferrin could improve the immune response to sublingually delivered antigen. Transferrin conjugated haemagglutinin induced a significant antibody and T cell response in both naïve animals and previously immunized animals. The immune response generated was able to protect mice against influenza virus challenge. Sublingually administered antigen dispersed more widely through the gastro-intestinal tract than intranasally delivered antigen and transferrin conjugation had a more marked effect on sublingually delivered antigen than intranasal immunisation. From these studies we conclude that transferrin conjugation of antigen is effective at boosting immune responses to sublingually delivered antigen and may be an attractive approach for influenza vaccines, particularly when mass campaigns are required.
Imperial College London, Mucosal Infection and Immunity, Section of Virology, St Mary's Campus, London W2 1PG, United Kingdom.
Jamie F S
JF
Mann
Imperial College London, Mucosal Infection and Immunity, Section of Virology, St Mary's Campus, London W2 1PG, United Kingdom.
John S
JS
Tregoning
Imperial College London, Mucosal Infection and Immunity, Section of Virology, St Mary's Campus, London W2 1PG, United Kingdom.
Yoann
Y
Aldon
Imperial College London, Mucosal Infection and Immunity, Section of Virology, St Mary's Campus, London W2 1PG, United Kingdom.
Robin J
RJ
Shattock
Imperial College London, Mucosal Infection and Immunity, Section of Virology, St Mary's Campus, London W2 1PG, United Kingdom. Electronic address: p.mckay@imperial.ac.uk.
Paul F
PF
McKay
D000281:Administration, Intranasal; D000286:Administration, Sublingual; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015703:Antigens, CD / Q000008:administration & dosage* / Q000737:chemistry; D005260:Female; D006389:Hemagglutinins, Viral / Q000008:administration & dosage* / Q000737:chemistry; D007074:Immunoglobulin G / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000737:chemistry; D008168:Lung / Q000821:virology; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011990:Receptors, Transferrin / Q000008:administration & dosage* / Q000737:chemistry; D013601:T-Lymphocytes / Q000276:immunology
D000914:Antibodies, Viral; D015703:Antigens, CD; C068126:CD71 antigen; D006389:Hemagglutinins, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D011990:Receptors, Transferrin
Immune response; Influenza; Oral; Sublingual; Targeting; Transferrin