Protection against cutaneous leishmaniasis by intranasal vaccination with lipophosphoglycan.
We previously showed the opposing effect of systemic and mucosal vaccination with whole Leishmania amazonensis antigen (LaAg). Here, the role played by lipophosphoglycan (LPG) as the key disease-promoting component of intramuscular (i.m.) LaAg and its usefulness as a defined intranasal vaccine was investigated in murine cutaneous leishmaniasis. BALB/c mice were twice vaccinated by the i.m. route with 25mug of intact LaAg or with LaAg that was pretreated with anti-LPG 3A1-La monoclonal antibody, prior to infection with L. amazonensis. LPG neutralization rendered the otherwise disease-promoting LaAg antigen protective, as observed by the smaller lesion sizes and reduced parasite burden. The increased resistance was accompanied by a markedly lower antigen-driven TGF-beta and IL-10 responses in the lesion-draining lymph nodes, concomitant with significantly higher IFN-gamma production. To test for intranasal efficacy, 10 microg of affinity-purified LPG and its parental LaAg were twice instilled in the nostrils prior to L. amazonensis infection. In both cases, similarly slower lesion growth and lower parasite burden were found that was associated with increased IFN-gamma and IL-10 responses in the lesion-draining lymph nodes. These results support a role for LPG in the dual route-related effect of LaAg and shows its strong potential as a defined needle-free and adjuvant-free vaccine for cutaneous leishmaniasis.
Pinheiro
Roberta Olmo
RO
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21949-900 Rio de Janeiro, RJ, Brazil.
Pinto
Eduardo Fonseca
EF
de Matos Guedes
Herbert Leonel
HL
Filho
Orlando Augusto Agrellos
OA
de Mattos
Katherine Antunes
KA
Saraiva
Elvira Maria
EM
de Mendonça
Sergio Coutinho Furtado
SC
Rossi-Bergmann
Bartira
B
D000281:Administration, Intranasal; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D006028:Glycosphingolipids / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D007894:Leishmania mexicana / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D016052:Protozoan Vaccines / Q000008:administration & dosage* / Q000276:immunology; D014611:Vaccination
D000953:Antigens, Protozoan; D006028:Glycosphingolipids; D016052:Protozoan Vaccines; C008290:lipophosphonoglycan; D007371:Interferon-gamma