title: A "prime-pull" vaccine strategy has a modest effect on local and systemic antibody responses to HIV gp140 in mice.
abstract: One potential strategy for the prevention of HIV infection is to induce virus specific mucosal antibody that can act as an immune barrier to prevent transmission. The mucosal application of chemokines after immunisation, termed "prime-pull", has been shown to recruit T cells to mucosal sites. We wished to determine whether this strategy could be used to increase B cells and antibody in the vaginal mucosa following immunisation with an HIV antigen. BALB/c mice were immunised intranasally with trimeric gp140 prior to vaginal application of the chemokine CCL28 or the synthetic TLR4 ligand MPLA, without antigen six days later. There was no increase in vaginal IgA, IgG or B cells following the application of CCL28, however vaginal application of MPLA led to a significant boost in antigen specific vaginal IgA. Follow up studies to investigate the effect of the timing of the "pull" stimulation demonstrated that when given 14 days after the initial immunisation MPLA significantly increased systemic antibody responses. We speculate that this may be due to residual inflammation prior to re-immunisation. Overall we conclude that in contrast to the previously observed effect on T cells, the use of "prime-pull" has only a modest effect on B cells and antibody.
authors.affiliation: Mucosal Infection & Immunity Group, Section of Infectious Diseases, Imperial College London, London, United Kingdom.
authors.forename: John S
authors.initials: JS
authors.lastname: Tregoning
authors.forename: Viviana
authors.initials: V
authors.lastname: Buffa
authors.forename: Anna
authors.initials: A
authors.lastname: Oszmiana
authors.forename: Katja
authors.initials: K
authors.lastname: Klein
authors.forename: Adam A
authors.initials: AA
authors.lastname: Walters
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Shattock
mesh_terms: D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000282:Administration, Intravaginal; D000818:Animals; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000008:administration & dosage / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015483:HIV Antibodies / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000276:immunology; D008050:Lipid A / Q000031:analogs & derivatives; D051379:Mice; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D015483:HIV Antibodies; D007070:Immunoglobulin A; D008050:Lipid A; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1; C048436:monophosphoryl lipid A