Changes in B Cell Pool of Patients With Multibacillary Leprosy: Diminished Memory B Cell and Enhanced Mature B in Peripheral Blood.

Despite being treatable, leprosy still represents a major public health problem, and many mechanisms that drive leprosy immunopathogenesis still need to be elucidated. B cells play important roles in immune defense, being classified in different subgroups that present distinct roles in the immune response. Here, the profile of B cell subpopulations in peripheral blood of patients with paucibacillary (TT/BT), multibacillary (LL/BL) and erythema nodosum leprosum was analyzed. B cell subpopulations (memory, transition, plasmablasts, and mature B cells) and levels of IgG were analyzed by flow cytometry and ELISA, respectively. It was observed that Mycobacterium leprae infection can alter the proportions of B cell subpopulations (increase of mature and decrease of memory B cells) in patients affected by leprosy. This modulation is associated with an increase in total IgG and the patient's clinical condition. Circulating B cells may be acting in the modulation of the immune response in patients with various forms of leprosy, which may reflect the patient's ability to respond to M. leprae.

Observational study on immune response to yellow fever and measles vaccines in 9 to 15-month old children. Is it necessary to wait 4 weeks between two live attenuated vaccines?

BACKGROUND: The use of 2 live attenuated vaccines (LAV) is recommended to be simultaneous or after an interval of at least four weeks between injections. The primary objective of this study was to compare the humoral response to yellow fever (YF) and measles vaccines among children vaccinated against these two diseases, either simultaneously or separated by an interval of 7-28 days. SUBJECTS AND METHODS: A prospective, multicenter observational study was conducted among children aged 9-15 months. The primary endpoint was the occurrence of positive yellow fever antibodies after YF vaccine by estimating the titers of neutralizing antibodies from venous blood samples. Children vaccinated against YF 7-28 days after receiving the vaccine against measles (test group) were compared with children vaccinated the same day against these two diseases (referent group). RESULTS: Analysis was performed on 284 children. Of them, fifty-four belonged to the test group. Measles serology was positive in 91.7% of children. Neutralizing antibodies against YF were detected in 90.7% of the test group and 92.9 of the referent group (p=0.6). In addition, quantitative analysis of the immune response did not show a lower response to YF vaccination when it took place 1-28 days after measles vaccination. DISCUSSION: In 1965, Petralli showed a lower response to the smallpox vaccine when injected 4-20 days after measles vaccination. Since then, recommendations are to observe an interval of four weeks between LAV not injected on the same day. Other published studies failed to show a significant difference in the immune response to a LAV injected 1-28 days after another LAV. These results suggest that the usual recommendations for immunization with two LAV may not be correct. CONCLUSION: In low income countries, the current policy should be re-evaluated. This re-evaluation should also be applied to travelers to yellow fever endemic countries.

Role of active and inactive cytotoxic immune response in human immunodeficiency virus dynamics.

OBJECTIVES: Mathematical models can be helpful to understand the complex dynamics of human immunodeficiency virus infection within a host. Most of work has studied the interactions of host responses and virus in the presence of active cytotoxic immune cells, which decay to zero when there is no virus. However, recent research highlights that cytotoxic immune cells can be inactive but never be depleted. METHODS: We propose a mathematical model to investigate the human immunodeficiency virus dynamics in the presence of both active and inactive cytotoxic immune cells within a host. We explore the impact of the immune responses on the dynamics of human immunodeficiency virus infection under different disease stages. RESULTS: Standard mathematical and numerical analyses are presented for this new model. Specifically, the basic reproduction number is computed and local and global stability analyses are discussed. CONCLUSION: Our results can give helpful insights when designing more effective drug schedules in the presence of active and inactive immune responses.

COMPARISON OF AGGLUTINATING AND GROWTH INHIBITION ANTIBODIES LEVELS IN SOWS IMMUNIZED WITH TWO EXPERIMENTAL INACTIVATED MONOVALENT VACCINES OF CANICOLA SEROVAR: WHOLE CULTURE WITH ALUMINUM HYDROXIDE AND LIPOPOLYSACCHARIDE SUBUNIT WITH LIPID A

ABSTRACT It was compared the antibody response of sows immunized with two experimental vaccines produced with L.interrogans, serovar Canicola, strain LO-4, isolated in Brazil.One of the vaccines was the usual bacterin (whole culture inactivated with phenol and adjuvanted with aluminum hydroxide -WC-AlOH3) and the other one was a subunit vaccine produced with a lipopolysaccharide (LPS) fraction extracted from the bacteria outer envelop and with the lipid A, also extracted from the leptospira wall as adjuvant (LPS-MPLA). Experiment was as follows: group 1 (n = 11), not immunized control, group 2, (n = 11): two immunization with 30 days interval of LPS-MPLA vaccine and group 3 (n = 11): two immunization with 30 days interval of WC-AlOH3 vaccine All three groups were simultaneously immunized, independently of pregnancy stage. Both agglutinin and neutralizing post vaccination antibodies levels were measured respectively by the microscopic sera agglutination with live antigens test (MAT) and the in vitro leptospira growth inhibition test (GIT). Sera collections were performed each 30 days during four months after the first vaccination. Non vaccinated control group animals presented no agglutinating antibodies against Canicola serovar during the whole experiment. At 32 and 68 post vaccination days the agglutinating antibodies levels of group 2 (LPS-MPLA) were significantly higher than the observed in group 3 (WC AlOH3), respectively, p = 0.013 and p = 0.031. The differences observed in the growth inhibition antibodies titers of the two vaccines tested were not significant (p > 0.05). Despite the peak of post-vaccination agglutinins have been registered at 68 days after first immunization, higher levels growth inhibition antibodies were detected at 30 days of first vaccination. Subunit vaccine presented the same immunogenic capacity for the production of neutralizing antibodies as the whole culture one.

RESUMO Foi comparada a resposta imune de fêmeas suínas adultas imunizadas contra a leptospirose, com vacinas monovalentes produzidas com L.interrogans, sorovar Canicola estirpe LO4, isolada no Brasil. A vacina foi empregada em duas formas: cultura de bactérias totais inativada e acrescida do adjuvante de hidróxido de alumínio (WC-AlOH3) e a do tipo de subunidade constituída apenas por uma fração de lipopolisacarídios (LPS) extraídos do envelope externo da bactéria tendo como adjuvante o monofosforil lipídio A, também extraído da parede da leptospira (LPS-MPLA). O delineamento experimental incluiu: grupo 1 (n = 11): controle não imunizado; grupo 2 (n = 11): imunizado com duas aplicações em intervalo de 30 dias da vacina LPS MFLA; Grupo 3 (n = 11): imunizado com duas aplicações em intervalo de 30 dias da vacina WC-AlOH3. Todos os grupos foram imunizados simultaneamente sem ser considerado o estágio de gestação dos animais. Os níveis de anticorpos pós-vacinais, aglutinantes e neutralizantes foram avaliados, respectivamente, pelos testes de soroaglutinação microscópica com antígenos vivos (SAM) e o de inibição do crescimento de leptospiras in vitro (ICLIV). O monitoramento sorológico foi efetuado a cada 30 dias durante quatro meses após aplicação da primeira dose da vacina. Os animais do grupo controle, não vacinados, não apresentaram anticorpos aglutinantes para o sorovar Canicola durante todo o período experimental. Aos 32 e 68 dias da primo-vacinação, os níveis de anticorpos aglutinantes do grupo 2 (LPS-MPLA) foram significativamente superiores aos observados no grupo 3 (WC AlOH3), respectivamente p = 0,013 e p = 0,031. As diferenças observadas nos níveis de anticorpos inibidores do crescimento de leptospiras in vitro, induzidos pelas duas vacinas, não foram significativas (p > 0,05). A despeito do pico de anticorpos aglutinantes pós-vacinais ter sido registrado aos 68 dias da primeira imunização, os níveis mais elevados de anticorpos inibidores do crescimento de leptospiras já foram observados aos 30 dias da primo-vacinação. A vacina de subunidade apresentou a mesma capacidade de indução de anticorpos neutralizantes que a vacina de bactérias totais.

Comparison of agglutinating and growth inhibition antibodies levels in sows immunized with two experimental inactivated monovalent vaccines of Canicola serovar: whole culture with aluminum hydroxide and lipopolysaccharide subunit with lipid A / Comparação dos níveis de anticorpos pós-vacinais, aglutinantes e inibidores do crescimento de leptospiras em fêmeas suínas imunizadas com duas vacinas inativadas experimentais monovalentes do sorovar Canicola: cultivo total inativado com hidróxido de alumínio e subunidade de lipopolissacarídios com monofosforil lipídio A

It was compared the antibody response of sows immunized with two experimental vaccines produced with L.interrogans, serovar Canicola, strain LO-4, isolated in Brazil.One of the vaccines was the usual bacterin (whole culture inactivated with phenol and adjuvanted with aluminum hydroxide -WC-AlOH3) and the other one was a subunit vaccine produced with a lipopolysaccharide (LPS) fraction extracted from the bacteria outer envelop and with the lipid A, also extracted from the leptospira wall as adjuvant (LPS-MPLA). Experiment was as follows: group 1 (n = 11), not immunized control, group 2, (n = 11): two immunization with 30 days interval of LPS-MPLA vaccine and group 3 (n = 11): two immunization with 30 days interval of WC-AlOH3 vaccine All three groups were simultaneously immunized, independently of pregnancy stage. Both agglutinin and neutralizing post vaccination antibodies levels were measured respectively by the microscopic sera agglutination with live antigens test (MAT) and the in vitro leptospira growth inhibition test (GIT). Sera collections were performed each 30 days during four months after the first vaccination. Non vaccinated control group animals presented no agglutinating antibodies against Canicola serovar during the whole experiment. At 32 and 68 post vaccination days the agglutinating antibodies levels of group 2 (LPS-MPLA) were significantly higher than the observed in group 3 (WC AlOH3), respectively, p = 0.013 and p = 0.031. The differences observed in the growth inhibition antibodies titers of the two vaccines tested were not significant (p > 0.05). Despite the peak of post-vaccination agglutinins have been registered at 68 days after first immunization, higher levels growth inhibition antibodies were detected at 30 days of first vaccination. Subunit vaccine presented the same immunogenic capacity for the production of neutralizing antibodies as the whole culture one.

Foi comparada a resposta imune de fêmeas suínas adultas imunizadas contra a leptospirose, com vacinas monovalentes produzidas com L.interrogans, sorovar Canicola estirpe LO4, isolada no Brasil. A vacina foi empregada em duas formas: cultura de bactérias totais inativada e acrescida do adjuvante de hidróxido de alumínio (WC-AlOH3) e a do tipo de subunidade constituída apenas por uma fração de lipopolisacarídios (LPS) extraídos do envelope externo da bactéria tendo como adjuvante o monofosforil lipídio A, também extraído da parede da leptospira (LPS-MPLA). O delineamento experimental incluiu: grupo 1 (n = 11): controle não imunizado; grupo 2 (n = 11): imunizado com duas aplicações em intervalo de 30 dias da vacina LPS MFLA; Grupo 3 (n = 11): imunizado com duas aplicações em intervalo de 30 dias da vacina WC-AlOH3. Todos os grupos foram imunizados simultaneamente sem ser considerado o estágio de gestação dos animais. Os níveis de anticorpos pós-vacinais, aglutinantes e neutralizantes foram avaliados, respectivamente, pelos testes de soroaglutinação microscópica com antígenos vivos (SAM) e o de inibição do crescimento de leptospiras in vitro (ICLIV). O monitoramento sorológico foi efetuado a cada 30 dias durante quatro meses após aplicação da primeira dose da vacina. Os animais do grupo controle, não vacinados, não apresentaram anticorpos aglutinantes para o sorovar Canicola durante todo o período experimental. Aos 32 e 68 dias da primo-vacinação, os níveis de anticorpos aglutinantes do grupo 2 (LPS-MPLA) foram significativamente superiores aos observados no grupo 3 (WC AlOH3), respectivamente p = 0,013 e p = 0,031. As diferenças observadas nos níveis de anticorpos inibidores do crescimento de leptospiras in vitro, induzidos pelas duas vacinas, não foram significativas (p > 0,05). A despeito do pico de anticorpos aglutinantes pós-vacinais ter sido registrado aos 68 dias da primeira imunização, os níveis mais elevados de anticorpos inibidores do crescimento de leptospiras já foram observados aos 30 dias da primo-vacinação. A vacina de subunidade apresentou a mesma capacidade de indução de anticorpos neutralizantes que a vacina de bactérias totais.