ABSTRACT
Objective: To understand the dynamics of Zika virus (ZIKV)-specific antibody immunity in children born to mothers in a flavivirus-endemic region during and after the emergence of ZIKV in the Americas. Methods: We performed serologic testing for ZIKV cross-reactive and type-specific IgG in two longitudinal cohorts, which enrolled pregnant women and their children (PW1 and PW2) after the beginning of the ZIKV epidemic in Nicaragua. Quarterly samples from children over their first two years of life and maternal blood samples at birth and at the end of the two-year follow-up period were studied. Results: Most mothers in this dengue-endemic area were flavivirus-immune at enrollment. ZIKV-specific IgG (anti-ZIKV EDIII IgG) was detected in 82 of 102 (80.4%) mothers in cohort PW1 and 89 of 134 (66.4%) mothers in cohort PW2, consistent with extensive transmission observed in Nicaragua during 2016. ZIKV-reactive IgG decayed to undetectable levels by 6-9 months in infants, whereas these antibodies were maintained in mothers at the year two time point. Interestingly, a greater contribution to ZIKV immunity by IgG3 was observed in babies born soon after ZIKV transmission. Finally, 43 of 343 (13%) children exhibited persistent or increasing ZIKV-reactive IgG at ≥9 months, with 10 of 30 (33%) tested demonstrating serologic evidence of incident dengue infection. Conclusions: These data inform our understanding of protective and pathogenic immunity to potential flavivirus infections in early life in areas where multiple flaviviruses co-circulate, particularly considering the immune interactions between ZIKV and dengue and the future possibility of ZIKV vaccination in women of childbearing potential. This study also shows the benefits of cord blood sampling for serologic surveillance of infectious diseases in resource-limited settings.
Subject(s)
Dengue Virus , Dengue , Flavivirus , Zika Virus Infection , Zika Virus , Infant , Infant, Newborn , Female , Humans , Child , Pregnancy , Child, Preschool , Nicaragua/epidemiology , Antibodies, Viral , Immunoglobulin G , Cross ReactionsABSTRACT
The limited ability of newborn piglets to produce cytokines may influence lymphocyte development and response to antigen exposure. As a result, colostrum intake is crucial because it contains nutrients that contribute to immune system development in piglets. Our goal was to investigate the effect of sow parity on the transfer of maternal cytokines to nursing piglets. Sixty piglets from nine sows were divided into six groups: piglets from gilts or sows kept with their dams and allowed to suckle normally; piglets from gilts or sows having their dams exchanged and then allowed to suckle normally; piglets from gilts or sows isolated from their dams and bottle-fed a commercial milk replacer formula for pigs. All piglets remained in the diet groups for 24 hours after birth. Concentrations of cytokines in colostrum and serum of gilt/ sows and serum of piglets were then evaluated. The 13 evaluated cytokines had higher concentrations in colostrum and serum of sows than in gilts. Concentrations of GM-CSF, IFNγ, IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-12, IL-18, and TNFα were higher in piglets suckling sows. Piglets that received commercial formula showed higher concentrations of the cytokines IL1-RA and IL-8 than piglets fed colostrum. This outcome can influence piglets' development into adulthood. In short, our findings demonstrated that maternal parity influenced colostrum cytokine composition and its maternal transfer patterns.(AU)
A capacidade limitada dos leitões recém-nascidos de produzir citocinas pode influenciar o desenvolvimento de linfócitos e a resposta à exposição ao antígeno. Portanto, a ingestão de colostro é importante porque contém nutrientes, que contribuem para o desenvolvimento do sistema imunológico do leitão. O objetivo do estudo foi investigar o efeito da paridade da porca na transferência de citocina materna para leitões lactentes. Sessenta leitões de nove porcas foram divididos em seis grupos: leitões de marrãs/porcas mantidas com suas próprias mães e amamentadas normalmente; leitões de marrãs/porcas que foram trocados de mães e amamentados normalmente; leitões de marrãs/porcas que foram isolados das mães e alimentados com mamadeira com substituto do leite para suínos. Os leitões permaneceram nos grupos por 24 horas após o nascimento. Foram avaliadas as concentrações de citocinas no colostro e plasma das marrãs/porcas e no plasma dos leitões. O colostro e o plasma das porcas apresentaram maiores concentrações das 13 citocinas analisadas do que as marrãs. No mesmo sentido, as concentrações de GM-CSF, IFNγ, IL-1α, IL-1ß, IL-2, IL-4, IL-6, IL-10, IL-12, IL-18 e TNFα foram significantemente maiores nos leitões que mamaram o colostro de porcas. Os leitões que receberam fórmula comercial apresentaram, em especial, concentrações das citocinas IL1-RA e IL-8 superiores aos leitões amamentados com colostro. Isso pode influenciar o desenvolvimento até a fase adulta. Portanto, nossos dados demonstraram que a paridade materna influenciou a composição das citocinas do colostro, bem como as características das citocinas na transferência materna.(AU)
Subject(s)
Animals , Female , Pregnancy , Parity/physiology , Swine/immunology , Cytokines/analysis , Immunization, Passive/veterinary , Colostrum/physiologyABSTRACT
Neonates are highly susceptible to intracellular pathogens, leading to high morbidity and mortality rates. CD8+ T lymphocytes are responsible for the elimination of infected cells. Understanding the response of these cells to normal and high stimulatory conditions is important to propose better treatments and vaccine formulations for neonates. We have previously shown that human neonatal CD8+ T cells overexpress innate inflammatory genes and have a low expression of cytotoxic and cell signaling genes. To investigate the activation potential of these cells, we evaluated the transcriptome of human neonatal and adult naïve CD8+ T cells after TCR/CD28 signals ± IL-12. We found that in neonatal cells, IL-12 signals contribute to the adult-like expression of genes associated with cell-signaling, T-cell cytokines, metabolism, and cell division. Additionally, IL-12 signals contributed to the downregulation of the neutrophil signature transcription factor CEBPE and other immaturity related genes. To validate the transcriptome results, we evaluated the expression of a series of genes by RT-qPCR and the promoter methylation status on independent samples. We found that in agreement with the transcriptome, IL-12 signals contributed to the chromatin closure of neutrophil-like genes and the opening of cytotoxicity genes, suggesting that IL-12 signals contribute to the epigenetic reprogramming of neonatal lymphocytes. Furthermore, high expression of some inflammatory genes was observed in naïve and stimulated neonatal cells, in agreement with the high inflammatory profile of neonates to infections. Altogether our results point to an important contribution of IL-12 signals to the reprogramming of the neonatal CD8+ T cells.
Subject(s)
CD8-Positive T-Lymphocytes/immunology , Cellular Reprogramming/immunology , Infant, Newborn/immunology , Interleukin-12/immunology , Humans , Signal Transduction/immunologyABSTRACT
Types C and D strains of Clostridium botulinum are commonly related to avian and mammalian botulism. Although there are numerous vaccine recommendations, little research has been conducted to indicate the real effectiveness of vaccine timing or the ideal immunization protocol for young beef calves. Four commercially available vaccines, two bivalent (Clostridium botulinum types C and D; vaccines 1 and 2) and two polyvalent (all Clostridium spp. including Clostridium botulinum types C and D; vaccines 3 and 4), that are currently used in Brazilian herds, were tested in order to verify the maternal immune response. One hundred cows, divided into four vaccinated groups and one unvaccinated group, were given a two-dose subcutaneous immunization, at day zero, followed by a second dose given at 42 days post-vaccination, which corresponded to 40 days before birth. Serum samples (n = 75) were collected only from healthy neonatal calves at 0, 7, 45 and 90 days post-calving (DPC) and subjected to indirect ELISA using the purified C and D holotoxins as capture antigens. The serological profile showed that all vaccines were able to induce a satisfactory neonatal immune response to both holotoxins at 7 DPC. However, at 45 and 90 DPC, a significant reduction (p < 0.05) was observed in the antibody level against C and D holotoxins in all tested vaccines. Neonatal immunization in calves is compromised by significant levels of maternal antibodies so that the necessity of planning a calf vaccination program involves assessment of disease risks at the production site.(AU)
Subject(s)
Animals , Allergy and Immunology/classification , Immunity, Maternally-Acquired/genetics , Cattle/classification , Toxoids , Botulism/pathology , Enzyme-Linked Immunosorbent AssayABSTRACT
Types C and D strains of Clostridium botulinum are commonly related to avian and mammalian botulism. Although there are numerous vaccine recommendations, little research has been conducted to indicate the real effectiveness of vaccine timing or the ideal immunization protocol for young beef calves. Four commercially available vaccines, two bivalent (Clostridium botulinum types C and D; vaccines 1 and 2) and two polyvalent (all Clostridium spp. including Clostridium botulinum types C and D; vaccines 3 and 4), that are currently used in Brazilian herds, were tested in order to verify the maternal immune response. One hundred cows, divided into four vaccinated groups and one unvaccinated group, were given a two-dose subcutaneous immunization, at day zero, followed by a second dose given at 42 days post-vaccination, which corresponded to 40 days before birth. Serum samples (n = 75) were collected only from healthy neonatal calves at 0, 7, 45 and 90 days post-calving (DPC) and subjected to indirect ELISA using the purified C and D holotoxins as capture antigens. The serological profile showed that all vaccines were able to induce a satisfactory neonatal immune response to both holotoxins at 7 DPC. However, at 45 and 90 DPC, a significant reduction (p < 0.05) was observed in the antibody level against C and D holotoxins in all tested vaccines. Neonatal immunization in calves is compromised by significant levels of maternal antibodies so that the necessity of planning a calf vaccination program involves assessment of disease risks at the production site. Finally, our findings represent the first demonstration of maternal immunity transferred to neonatal beef calves, including immunity levels after vaccination against Clostridium botulinum toxoids C and D.
Subject(s)
Animals , Cattle , Cattle , Cattle Diseases , Clostridium botulinum/virology , Immunity , Botulinum Toxins/antagonists & inhibitors , BrazilABSTRACT
Eighty-eight healthy crossbred holstein-zebu (HZ) dairy cows were distributed in four groups as follow: Group 1 = less than 70% HZ (19 cows); Group 2 = 75% HZ animals, corresponding to ¾ HZ (46 cows); Group 3 = crossbred animals between 80 to 90% HZ, corresponding to 13/16 HZ and 7/8 HZ (11 cows); Group 4 = cows more than 90% HZ (12 animals). After birth, colostrum samples were obtained from each cow and than were analyzed for immunoglobulin G (IgG) concentration by single radial immunodifusion assay. IgG colostral concentrations were not influenced by group of crossbred HZ and its mean concentration (145.97mg/m img src="http:/img/fbpe/cr/v31n6/a19img01.gif">) were higher than that related for purebreds Bos taurus dairy cows. Considering these results, it was concluded that artificial methods of feeding colostrum to crossbred HZ calves are not necessary. Probably, assisted natural sucking as soon after birth as possible is enough to get passive immune transfer.
Oitenta e oito vacas leiteiras mestiças holandês-zebu (HZ) foram distribuídas de acordo com a percentagem de grau de sangue holandês em quatro grupos: Grupo 1 = animais com menos de 70% de grau de sangue holandês (19 vacas); Grupo 2 = animais com 75% de grau de sangue holandês, que equivale a ¾ HZ (46 vacas); Grupo 3 = mestiços entre 80 e 90% de grau de sangue holandês, que corresponderam a 13/16 HZ e 7/8 HZ (11 vacas); Grupo 4 = vacas com mais de 90% de grau de sangue holandês (12 vacas). Após o parto, amostras de colostro da primeira ordenha foram colhidas e, posteriormente, submetidas à imunodifusão radial simples para determinações dos níveis de imunoglobulinas G (IgG). Os resultados obtidos permitiram concluir que as concentrações de IgG não são influenciadas pelos graus de sangue estudados e seus valores médios (145,94mg/m img src="http:/img/fbpe/cr/v31n6/a19img01.gif">) são muito superiores aos relatados para animais de raças taurinas puras. Por esse motivo, não se justifica o emprego de métodos artificiais de fornecimento do colostro em se tratando de mestiços HZ. Ademais, o nível elevado de IgG observado no colostro sugere que a adoção da prática da mamada natural assistida seja adequada para assegurar que, na maioria das vezes, os neonatos não venham a apresentar falhas de transferência de imunidade passiva.
ABSTRACT
Eighty-eight healthy crossbred holstein-zebu (HZ) dairy cows were distributed in four groups as follow: Group 1 = less than 70% HZ (19 cows); Group 2 = 75% HZ animals, corresponding to ¾ HZ (46 cows); Group 3 = crossbred animals between 80 to 90% HZ, corresponding to 13/16 HZ and 7/8 HZ (11 cows); Group 4 = cows more than 90% HZ (12 animals). After birth, colostrum samples were obtained from each cow and than were analyzed for immunoglobulin G (IgG) concentration by single radial immunodifusion assay. IgG colostral concentrations were not influenced by group of crossbred HZ and its mean concentration (145.97mg/m img src="http:/img/fbpe/cr/v31n6/a19img01.gif">) were higher than that related for purebreds Bos taurus dairy cows. Considering these results, it was concluded that artificial methods of feeding colostrum to crossbred HZ calves are not necessary. Probably, assisted natural sucking as soon after birth as possible is enough to get passive immune transfer.
Oitenta e oito vacas leiteiras mestiças holandês-zebu (HZ) foram distribuídas de acordo com a percentagem de grau de sangue holandês em quatro grupos: Grupo 1 = animais com menos de 70% de grau de sangue holandês (19 vacas); Grupo 2 = animais com 75% de grau de sangue holandês, que equivale a ¾ HZ (46 vacas); Grupo 3 = mestiços entre 80 e 90% de grau de sangue holandês, que corresponderam a 13/16 HZ e 7/8 HZ (11 vacas); Grupo 4 = vacas com mais de 90% de grau de sangue holandês (12 vacas). Após o parto, amostras de colostro da primeira ordenha foram colhidas e, posteriormente, submetidas à imunodifusão radial simples para determinações dos níveis de imunoglobulinas G (IgG). Os resultados obtidos permitiram concluir que as concentrações de IgG não são influenciadas pelos graus de sangue estudados e seus valores médios (145,94mg/m img src="http:/img/fbpe/cr/v31n6/a19img01.gif">) são muito superiores aos relatados para animais de raças taurinas puras. Por esse motivo, não se justifica o emprego de métodos artificiais de fornecimento do colostro em se tratando de mestiços HZ. Ademais, o nível elevado de IgG observado no colostro sugere que a adoção da prática da mamada natural assistida seja adequada para assegurar que, na maioria das vezes, os neonatos não venham a apresentar falhas de transferência de imunidade passiva.