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1.
J Leukoc Biol ; 96(6): 957-67, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25114162

RESUMO

Whereas infection or immunization of humans/primates with microbes coproducing HMBPP/IPP can remarkably activate Vγ2Vδ2 T cells, in vivo studies have not been done to dissect HMBPP- and IPP-driven expansion, pulmonary trafficking, effector functions, and memory polarization of Vγ2Vδ2 T cells. We define these phosphoantigen-host interplays by comparative immunizations of macaques with the HMBPP/IPP-coproducing Listeria ΔactA prfA* and HMBPP-deficient Listeria ΔactA ΔGCPE: prfA* mutant. The HMBPP-deficient ΔGCPE: mutant shows lower ability to expand Vγ2Vδ2 T cells in vitro than the parental HMBPP-producing strain but displays comparably attenuated infectivity or immunogenicity. Respiratory immunization of macaques with the HMBPP-deficient mutant elicits lower pulmonary and systemic responses of Vγ2Vδ2 T cells compared with the HMBPP-producing vaccine strain. Interestingly, HMBPP-deficient mutant reimmunization or boosting elicits enhanced responses of Vγ2Vδ2 T cells, but the magnitude is lower than that by HMBPP-producing listeria. HMBPP-deficient listeria differentiated fewer Vγ2Vδ2 T effector cells capable of coproducing IFN-γ and TNF-α and inhibiting intracellular listeria than HMBPP-producing listeria. Furthermore, HMBPP deficiency in listerial immunization influences memory polarization of Vγ2Vδ2 T cells. Thus, both HMBPP and IPP production in listerial immunization or infection elicit systemic/pulmonary responses and differentiation of Vγ2Vδ2 T cells, but a role for HMBPP is more dominant. Findings may help devise immune intervention.


Assuntos
Antígenos de Bactérias/imunologia , Vacinas Bacterianas/imunologia , Imunização , Memória Imunológica/imunologia , Listeria monocytogenes/imunologia , Listeriose/imunologia , Pulmão/imunologia , Organofosfatos/imunologia , Subpopulações de Linfócitos T/imunologia , Animais , Proteínas de Bactérias/genética , Líquido da Lavagem Broncoalveolar/imunologia , Células Cultivadas , Citocinas/análise , Enzimas/deficiência , Enzimas/genética , Interferon gama/biossíntese , Listeria monocytogenes/genética , Listeria monocytogenes/crescimento & desenvolvimento , Listeria monocytogenes/patogenicidade , Listeriose/prevenção & controle , Macaca mulatta , Macrófagos/microbiologia , Camundongos , Camundongos Endogâmicos BALB C , Fatores de Terminação de Peptídeos/deficiência , Fatores de Terminação de Peptídeos/genética , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Vacinas Atenuadas/imunologia , Virulência/genética
2.
J Infect Dis ; 208(2): 260-70, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23568175

RESUMO

Whether vaccination against a virus can protect against more virulent coinfection with the virus and additional pathogen(s) remains poorly characterized. Overlapping endemicity of human immunodeficiency virus (HIV) and malaria suggests that HIV/malaria coinfection frequently complicates acute and chronic HIV infection. Here we showed that vaccination of macaques with recombinant Listeria ΔactA prfA* expressing simian/human immunodeficiency virus (SHIV) gag and env elicited Gag- and Env-specific T-cell responses, and protected against life-threatening SHIV-related malaria after SHIV/Plasmodium fragile coinfection. SHIV antigen immunization reduced peak viremia, resisted SHIV/malaria-induced lymphoid destruction, and blunted coinfection-accelerated decline of CD4(+) T-cell counts after SHIV/malaria coinfection. SHIV antigen immunization also weakened coinfection-driven overreactive proinflammatory interferon-γ (IFNγ) responses and led to developing T helper cell 17/22 (Th17/Th22) responses after SHIV/malaria coinfection. The findings suggest that vaccination against AIDS virus can alter patterns of immune responses to the SHIV/malaria coinfection and protect against life-threatening SHIV-related malaria.


Assuntos
Antígenos Virais/imunologia , Coinfecção/imunologia , Infecções por HIV/imunologia , Malária/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Coinfecção/microbiologia , Coinfecção/parasitologia , Coinfecção/prevenção & controle , Produtos do Gene env/imunologia , Produtos do Gene gag/imunologia , Infecções por HIV/parasitologia , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , HIV-1/imunologia , Macaca mulatta/imunologia , Macaca mulatta/microbiologia , Macaca mulatta/virologia , Malária/microbiologia , Malária/prevenção & controle , Plasmodium/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Linfócitos T Auxiliares-Indutores/imunologia , Vacinação/métodos , Vacinas Sintéticas/imunologia
3.
Clin Vaccine Immunol ; 18(4): 640-6, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21270282

RESUMO

We previously showed that recombinant (r) Listeria monocytogenes carrying ΔactA and a selected prfA* mutation (r-Listeria ΔactA prfA*) secreted >100-fold more immunogen in broth culture than wild-type r-Listeria or r-Listeria ΔactA and elicited much greater cellular and humoral immune responses than r-Listeria ΔactA after intravenous vaccination of mice. Here, we conducted comparative studies evaluating vaccine-elicited immune responses in systemic and mucosal sites after intranasal, intravenous, intraperitoneal, or subcutaneous immunization of mice with r-Listeria ΔactA prfA* vaccine candidates. Intranasal vaccination of mice with r-Listeria ΔactA prfA* vaccine candidates elicited a robust gamma interferon-positive (IFN-γ(+)) cellular response in systemic sites, although intravenous or intraperitoneal immunization was more efficient. Surprisingly, intranasal vaccination elicited an appreciable pulmonary IFN-γ(+) cellular response that was nonstatistically higher than the magnitude induced by the intravenous route but was significantly greater than that elicited by subcutaneous immunization. Furthermore, although intranasal r-Listeria ΔactA prfA* delivery induced poor systemic IgG responses, intranasal vaccination elicited appreciable secretory immunogen-specific IgA titers that were similar to or higher in mucosal fluid than those induced by subcutaneous and intravenous immunizations. Thus, intranasal vaccination with r-Listeria ΔactA prfA* appears to be a useful approach for eliciting robust systemic and pulmonary cellular responses and measurable secretory mucosal IgA titers.


Assuntos
Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/imunologia , Imunoglobulina A Secretora/análise , Listeria monocytogenes/imunologia , Pulmão/imunologia , Vacinação/métodos , Administração Intranasal , Animais , Proteínas de Bactérias/genética , Vacinas Bacterianas/administração & dosagem , Feminino , Injeções Intraperitoneais , Injeções Intravenosas , Injeções Subcutâneas , Listeria monocytogenes/genética , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Fatores de Terminação de Peptídeos/genética , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia
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