Poly I:C elicits broader and stronger humoral and cellular responses to a Plasmodium vivax circumsporozoite protein malaria vaccine than Alhydrogel in mice.

Malaria remains a global health challenge, necessitating the development of effective vaccines. The RTS,S vaccination prevents Plasmodium falciparum (Pf) malaria but is ineffective against Plasmodium vivax (Pv) disease. Herein, we evaluated the murine immunogenicity of a recombinant PvCSP incorporating prevalent polymorphisms, adjuvanted with Alhydrogel or Poly I:C. Both formulations induced prolonged IgG responses, with IgG1 dominance by the Alhydrogel group and high titers of all IgG isotypes by the Poly I:C counterpart. Poly I:C-adjuvanted vaccination increased splenic plasma cells, terminally-differentiated memory cells (MBCs), and precursors relative to the Alhydrogel-combined immunization. Splenic B-cells from Poly I:C-vaccinated mice revealed an antibody-secreting cell- and MBC-differentiating gene expression profile. Biological processes such as antibody folding and secretion were highlighted by the Poly I:C-adjuvanted vaccination. These findings underscore the potential of Poly I:C to strengthen immune responses against Pv malaria.

Experiência inicial com a extensão de cateter-guia ExpressmanTM em um centro terciário de cardiologia de alto volume / Initial experience with the ExpressmanTM guide catheter extension in a high-volume tertiary cardiology center

Introdução: As extensões de cateter-guia fornecem maior suporte em intervenções coronárias percutâneas complexas. O ExpressmanTM é uma nova extensão de cateter-guia, e nosso objetivo foi avaliar o impacto de seu uso no sucesso do procedimento e nas complicações ocorridas em um centro de referência de alto volume. Métodos: Analisamos os dados de todos os procedimentos consecutivos em que foi usada uma extensão de cateter-guia ExpressmanTM. A decisão de usar uma extensão de cateter-guia ficou a critério do operador. O sucesso do dispositivo foi definido como o posicionamento bem-sucedido da extensão de cateter-guia dentro do vaso coronário, e o sucesso do procedimento foi definido como <20% de estenose residual e fluxo TIMI 3, sem perda significativa de ramos laterais. Eventos adversos cardíacos e cerebrovasculares maiores foram definidos como a combinação morte por todas as causas, infarto do miocárdio, revascularização do vaso-alvo e acidente vascular cerebral. Resultados: Foram incluídos 34 procedimentos entre abril de 2022 e janeiro de 2023. A maioria dos pacientes era do sexo masculino (59%), e a média de idade foi 66,5 anos. O uso da extensão de cateter-guia não foi planejado antes do procedimento em 17 procedimentos (50%). Os motivos mais comuns para o uso da extensão de cateter-guia foram angulação ou tortuosidade do vaso-alvo e posição desfavorável do óstio coronário. O sucesso do dispositivo foi obtido em 88% e o da revascularização, em 91%. Houve três oclusões de ramo lateral. Durante o acompanhamento clínico intra-hospitalar, não ocorreram sangramento e nem eventos adversos cardíacos e cerebrovasculares maiores. Conclusão: O sucesso do dispositivo e do procedimento foi alto, e a taxa de complicações foi baixa. O uso da extensão de cateter-guia como técnica de resgate em anatomias complexas permitiu o sucesso do procedimento na maioria dos pacientes que, de outro modo, não poderiam ser tratados.

Background: Guide catheter extensions provide increased support in complex percutaneous coronary interventions. The ExpressmanTM is a novel guide catheter extension and the objective was to assess the impact of its use on procedural success and complications in a high-volume reference center. Methods: We analyzed data from all consecutive procedures in which the ExpressmanTM guide catheter extension was used. The decision to use a guide catheter extension was at operator's discretion. Device success was defined as the successful positioning of the guide catheter extension in the coronary vessel and procedural success was defined as <20% residual stenosis and TIMI 3 flow, with no loss of significant side branches. Major adverse cardiac and cerebrovascular events were defined as the composite of all-cause death, myocardial infarction, target vessel revascularization and stroke. Results: From April 2022 to January 2023, 34 procedures were included. The majority of the patients were male (59%) and the mean age was 66.5 years. Guide catheter extension use was not planned pre-procedure in 17 procedures (50%). The most common reasons for guide catheter extension use were target vessel angulation or tortuosity and unfavorable coronary ostium position. Device success was obtained in 88% and revascularization success in 91%. There were three side branch occlusions. During in-hospital clinical follow-up, no major adverse cardiac and cerebrovascular events or major bleeding occurred. Conclusion: The device success and procedural success were high and the rate of complications was low. Guide catheter extension use as bailout technique in complex anatomies allowed procedural success in the vast majority of otherwise untreatable patients.

CCR6 expression reduces mouse survival upon malarial challenge with Plasmodium berghei NK65 strain.

BACKGROUND: It has been demonstrated that proteins expressed by liver-stage Plasmodium parasites can inhibit the translocation of transcription factors to the nucleus of different cells. This process would hinder the expression of immune genes, such as the CCL20 chemokine. OBJECTIVE: Since CCR6 is the only cognate receptor for CCL20, we investigated the importance of this chemokine-receptor axis against rodent malaria. METHODS: CCR6-deficient (KO) and wild-type (WT) C57BL/6 mice were challenged with Plasmodium berghei (Pb) NK65 sporozoites or infected red blood cells (iRBCs). Liver parasitic cDNA, parasitemia and serum cytokine concentrations were respectively evaluated through reverse transcription-polymerase chain reaction (RT-PCR), staining thin-blood smears with Giemsa solution, and enzyme-linked immunosorbent assay (ELISA). FINDINGS: Although the sporozoite challenges yielded similar liver parasitic cDNA and parasitemia, KO mice presented a prolonged survival than WT mice. After iRBC challenges, KO mice kept displaying higher survival rates as well as a decreased IL-12 p70 concentration in the serum than WT mice. CONCLUSION: Our data suggest that malaria triggered by PbNK65 liver- or blood-stage forms elicit a pro-inflammatory environment that culminates with a decreased survival of infected C57BL/6 mice.

In Vitro Generation of Human Antibody-Secreting Cells Through the Stimulation of PBMCs with Dengue Virus Particles.

The Dengue pathophysiology has had several aspects determined over the years. However, some points remain elusive, such as the metabolic factors that regulate the massive B cell differentiation into antibody-secreting cells observed in Dengue patients. In this chapter, we describe an in vitro method capable of mimicking this Dengue-induced cell expansion. More specifically, this approach allows dengue virus-stimulated peripheral blood mononuclear cells (PBMCs) from healthy individuals to enhance the frequency of phenotypical and functional antibody-secreting cells (ASCs) after 7 days of culture. A manuscript recently published by Bonezi and colleagues displays results generated through this methodology.

CCR6 expression reduces mouse survival upon malarial challenge with Plasmodium berghei NK65 strain

BACKGROUND It has been demonstrated that proteins expressed by liver-stage Plasmodium parasites can inhibit the translocation of transcription factors to the nucleus of different cells. This process would hinder the expression of immune genes, such as the CCL20 chemokine. OBJECTIVE Since CCR6 is the only cognate receptor for CCL20, we investigated the importance of this chemokine-receptor axis against rodent malaria. METHODS CCR6-deficient (KO) and wild-type (WT) C57BL/6 mice were challenged with Plasmodium berghei (Pb) NK65 sporozoites or infected red blood cells (iRBCs). Liver parasitic cDNA, parasitemia and serum cytokine concentrations were respectively evaluated through reverse transcription-polymerase chain reaction (RT-PCR), staining thin-blood smears with Giemsa solution, and enzyme-linked immunosorbent assay (ELISA). FINDINGS Although the sporozoite challenges yielded similar liver parasitic cDNA and parasitemia, KO mice presented a prolonged survival than WT mice. After iRBC challenges, KO mice kept displaying higher survival rates as well as a decreased IL-12 p70 concentration in the serum than WT mice. CONCLUSION Our data suggest that malaria triggered by PbNK65 liver- or blood-stage forms elicit a pro-inflammatory environment that culminates with a decreased survival of infected C57BL/6 mice.

Alternative Formulation of Antenna Arrays for DF Systems Considering Active-Element Patterns and Scattering Matrices.

Direction finding (DF) systems are used to determine the direction-of-arrival (DoA) of electromagnetic waves, thus allowing for the tracking of RF sources. In this paper, we present an alternative formulation of antenna arrays for modeling DF systems. To improve the accuracy of the data provided by the DF systems, the effects of mutual coupling in the array, polarization of the received waves, and impedance mismatches in the RF front-end receiver are all taken into account in the steering vectors of the DoA algorithms. A closed-form expression, which uses scattering parameter data and active-element patterns, is derived to compute the receiver output voltages. Special attention is given to the analysis of wave polarization relative to the DF system orientation. Applying the formulation introduced here, a complete characterization of the received waves is accomplished without the need for system calibration techniques. The validation of the proposed model is carried out by measurements of a 2.2 GHz DF system running a MUSIC algorithm. Tests are performed with a linear array of printed monopoles and with a planar microstrip antenna array having polarization diversity. The experimental results show DoA estimation errors below 6° and correct classification of the polarization of incoming waves, confirming the good performance of the developed formulation.

Hydroquinone Exposure Worsens Rheumatoid Arthritis through the Activation of the Aryl Hydrocarbon Receptor and Interleukin-17 Pathways.

Rheumatoid arthritis (RA) development is strongly associated with cigarette smoke exposure, which activates the aryl hydrocarbon receptor (AhR) as a trigger for Th17 inflammatory pathways. We previously demonstrated that the exposure to hydroquinone (HQ), one of the major compounds of cigarette tar, aggravates the arthritis symptomatology in rats. However, the mechanisms related to the HQ-related RA still remain elusive. Cell viability, cytokine secretion, and gene expression were measured in RA human fibroblast-like synoviocytes (RAHFLS) treated with HQ and stimulated or not with TNF-α. Antigen-induced arthritis (AIA) was also elicited in wild type (WT), AhR -/- or IL-17R -/- C57BL/6 mice upon daily exposure to nebulized HQ (25ppm) between days 15 to 21. At day 21, mice were challenged with mBSA and inflammatory parameters were assessed. The in vitro HQ treatment up-regulated TNFR1, TNFR2 expression, and increased ROS production. The co-treatment of HQ and TNF-α enhanced the IL-6 and IL-8 secretion. However, the pre-incubation of RAHFLS with an AhR antagonist inhibited the HQ-mediated cell proliferation and gene expression profile. About the in vivo approach, the HQ exposure worsened the AIA symptoms (edema, pain, cytokines secretion and NETs formation) in WT mice. These AIA effects were abolished in HQ-exposed AhR -/- and IL-17R -/- animals though. Our data demonstrated the harmful HQ influence over the onset of arthritis through the activation and proliferation of synoviocytes. The HQ-related RA severity was also associated with the activation of AhR and IL-17 pathways, highlighting how cigarette smoke compounds can contribute to the RA progression.

Viremia controls Env-specific antibody-secreting cell responses in simian immunodeficiency virus infected macaques pre and post-antiretroviral therapy.

OBJECTIVE: The aim of this study was to investigate the kinetics of Env (gp140)-specific antibody-secreting cells (ASCs) during acute and early chronic simian immunodeficiency virus (SIV) infection, and prior to and postantiretroviral therapy (ART) in rhesus macaques. DESIGN AND METHODS: At week 0, rhesus macaques were inoculated intravenously with SIVmac239 and the viral loads were allowed to develop. Daily ART was initiated at week 5 post infection until week 18, though the animals were monitored until week 28 for the following parameters: enumeration of SIV gp140-specific ASCs by ELISPOT; quantification of viremia and SIV gp140-specific IgG titres through qRT-PCR and ELISA, respectively; estimation of monocytes, follicular helper T cells (Tfh) and memory B cell frequencies using polychromatic flow cytometry. RESULTS: Direct correlations were consistently found between blood SIV gp140-specific ASC responses and viremia or SIV Env-specific IgG titres. In contrast, SIV gp140-specific ASC responses showed inverse correlations with the percentage of total memory B cells in the blood. In lymph nodes, the magnitude of the SIV gp140-specific ASC responses also followed the viral load kinetics. In contrast, the number of SIV gp140-specific ASCs presented did not correlate with frequencies of circulating activated monocyte (CD14+CD16+) or Tfh cells. CONCLUSION: Blood and/or lymph node viral loads may regulate the onset and magnitude of SIV gp140-specific ASCs during SIV infection and following ART in rhesus macaques.

Antibodies Against the Plasmodium vivax Apical Membrane Antigen 1 From the Belem Strain Share Common Epitopes Among Other Worldwide Variants.

Malaria is a human parasitic disease distributed in many tropical countries and caused by various Plasmodium species. Plasmodium vivax has the largest geographical distribution of the Plasmodium species and is predominant in the Americas, including Brazil. Only a small number of P. vivax vaccine formulations have successfully reached clinical trials relative to their P. falciparum counterparts. One of the candidate antigens for a blood-stage P. vivax vaccine is apical membrane antigen 1 (PvAMA-1). Due to the worldwide distribution of Plasmodium parasites, a high degree of variability has been detected in this antigen sequence, representing a considerable challenge to the development of a universal vaccine against malaria. In this study, we evaluated how PvAMA-1 polymorphisms influence vaccine-derived immune responses in P. vivax malaria. To this end, we expressed 9 recombinant protein representatives of different PvAMA-1 allelic variants in the yeast Pichia pastoris: Belem, Chesson I, Sal-1, Indonesia XIX, SK0814, TC103, PNG_05_ESP, PNG_62_MU, and PNG_68_MAS. After protein expression and purification, we evaluated the breadth of the immune responses derived from malaria-exposed individuals from the Amazon region. From 611 serum samples of malaria-exposed individuals, 53.68% of them reacted against the PvAMA-1 Belem through ELISA. Positive samples were further tested against recombinant proteins representing the other PvAMA-1 allelic variants. Whereas Sal-1, Chesson I and SK0814 variants were highly recognized by tested serum samples, Indonesia XIX, TC103, PNG_05_ESP, PNG_62_MU, and PNG_68_MAS were only slightly recognized. Moreover, polyclonal sera derived from C57BL/6 mice immunized with the PvAMA-1 Belem protein predominantly recognized Belem, Sal-1, Chesson I, SK0814, and Indonesia XIX through ELISA. Last, ELISA-based competition assays demonstrated that a previous interaction between anti-Belem polyclonal serum and Sal-1, Chesson I, SK0814, or Indonesia XIX proteins could further inhibit antibody binding to the Belem variant. Our human and mouse data suggest the presence of common epitopes or cross-reactivity between Belem, Sal-1, Chesson I, and SK0814 variants. Although the PvAMA-1 Belem variant induces strain-transcendent antibodies, PvAMA-1 variants from Thailand and Papua New Guinea may need to be included in a universal vaccine formulation to achieve protection against P. vivax malaria.

Gestational trophoblastic neoplasia lethality among Brazilian women: A retrospective national cohort study.

OBJECTIVE: To investigate GTN lethality among Brazilian women comparing cases of death by GTN with those who survived, thereby identifying factors associated with GTN lethality. METHODS: We retrospectively reviewed medical records of women with GTN treated at ten Brazilian GTN Reference Centers, from January 1960 to December 2017. We evaluated factors associated with death from GTN and used Cox proportional hazards regression models to identify independent variables with significant influence on the risk of death. RESULTS: From 2186 patients with GTN included in this study, 2092 (95.7%) survived and 89 (4%) died due to GTN. When analyzing the relative risk (RR), adjusted for WHO/FIGO score, patients with low risk disease had a significantly higher risk of death if they had choriocarcinoma (RR: 12.40), metastatic disease (RR: 12.57), chemoresistance (RR: 3.18) or initial treatment outside the Reference Center (RR: 12.22). In relation to patients with high-risk GTN, these factors were significantly associated with death due to GTN: the time between the end of antecedent pregnancy and the initiation of chemotherapy (RR: 4.10), metastatic disease (RR: 14.66), especially in brain (RR: 8.73) and liver (RR: 5.76); absence of chemotherapy or initial treatment with single agent chemotherapy (RR: 10.58 and RR: 1.81, respectively), chemoresistance (RR: 3.20) and the initial treatment outside the Reference Center (RR: 28.30). CONCLUSION: The risk of mortality from low and high-risk GTN can be reduced by referral of these patients to a Reference Center or, if not possible, to involve clinicians in a Reference Center with consultation regarding management.

São Paulo School of Advanced Sciences on Vaccines: an overview.

Two years ago, we held an exciting event entitled the São Paulo School of Advanced Sciences on Vaccines (SPSASV). Sixty-eight Ph.D. students, postdoctoral fellows and independent researchers from 37 different countries met at the Mendes Plaza Hotel located in the city of Santos, SP - Brazil to discuss the challenges and the new frontiers of vaccinology. The SPSASV provided a critical and comprehensive view of vaccine research from basics to the current state-of-the-art techniques performed worldwide. For 10 days, we discussed all the aspects of vaccine development in 36 lectures, 53 oral presentations and 2 poster sessions. At the end of the course, participants were further encouraged to present a model of a grant proposal related to vaccine development against individual pathogens. Among the targeted pathogens were viruses (Chikungunya, HIV, RSV, and Influenza), bacteria (Mycobacterium tuberculosis and Streptococcus pyogenes), parasites (Plasmodium falciparum or Plasmodium vivax), and the worm Strongyloides stercoralis. This report highlights some of the knowledge shared at the SPSASV.

Protective Malaria Vaccine in Mice Based on the Plasmodium vivax Circumsporozoite Protein Fused with the Mumps Nucleocapsid Protein.

Plasmodium vivax is the most common species of human malaria parasite found outside Africa, with high endemicity in Asia, Central and South America, and Oceania. Although Plasmodium falciparum causes the majority of deaths, P. vivax can lead to severe malaria and result in significant morbidity and mortality. The development of a protective vaccine will be a major step toward malaria elimination. Recently, a formulation containing the three allelic variants of the P. vivax circumsporozoite protein (PvCSP-All epitopes) showed partial protection in mice after a challenge with the hybrid Plasmodium berghei (Pb) sporozoite, in which the PbCSP central repeats were replaced by the VK210 PvCSP repeats (Pb/Pv sporozoite). In the present study, the chimeric PvCSP allelic variants (VK210, VK247, and P. vivax-like) were fused with the mumps virus nucleocapsid protein in the absence (NLP-CSPR) or presence of the conserved C-terminal (CT) domain of PvCSP (NLP-CSPCT). To elicit stronger humoral and cellular responses, Pichia pastoris yeast was used to assemble them as nucleocapsid-like particles (NLPs). Mice were immunized with each recombinant protein adjuvanted with Poly (I:C) and presented a high frequency of antigen-specific antibody-secreting cells (ASCs) on days 5 and 30, respectively, in the spleen and bone marrow. Moreover, high IgG titers against all PvCSP variants were detected in the sera. Later, these immunized mice with NLP-CSPCT were challenged with Pb/Pv sporozoites. Sterile protection was observed in 30% of the challenged mice. Therefore, this vaccine formulation use has the potential to be a good candidate for the development of a universal vaccine against P. vivax malaria.

Coordination among Bond Formation/Cleavage in a Bifunctional-Catalyzed Fast Amide Hydrolysis: Evidence for an Optimized Intramolecular N-Protonation Event.

A density functional theory (DFT) computational analysis, using the ωB97X-D functional, of a rapid amide cleavage in 2-carboxyphthalanilic acid (2CPA), where the amide group is flanked by two catalytic carboxyls, reveals key mechanistic information: (a) General base catalysis by a carboxylate coupled to general acid catalysis by a carboxyl is not operative. (b) Nucleophilic attack by a carboxylate on the amide carbonyl coupled to general acid catalysis at the amide oxygen can also be ruled out. (c) A mechanistic pathway that remains viable involves general acid proton delivery to the amide nitrogen by a carboxyl, while the other carboxylate engages in nucleophilic attack upon the amide carbonyl; a substantially unchanged amide carbonyl in the transition state; two concurrent bond-forming events; and a spatiotemporal-base rate acceleration. This mechanism is supported by molecular dynamic simulations which confirm a persistent key intramolecular hydrogen bonding. These theoretical conclusions, although not easily verified by experiment, are consistent with a bell-shaped pH/rate profile but are at odds with hydrolysis mechanisms in the classic literature.

Flavivirus-Mediating B Cell Differentiation Into Antibody-Secreting Cells in Humans Is Associated With the Activation of the Tryptophan Metabolism.

Patients infected with the Dengue virus (DENV) often present with a massive generation of DENV-specific antibody-secreting cells (ASCs) in the blood. In some cases, these ASCs represent more than 50% of the circulating B cells, a higher magnitude than those induced by other infections, vaccinations, and plasma cell lymphomas. However, it remains unclear how the DENV infection elicits this colossal response. To address this issue, we utilised an in vitro strategy to induce human PBMCs of healthy individuals incubated with DENV particles (DENV4 TVP/360) to differentiate into ASCs. As controls, PBMCs were incubated with a mitogen cocktail or supernatants of uninfected C6/36 cells (mock). The ASC phenotype and function were increasingly detected in the DENV and mitogen-cultured PBMCs as compared to mock-treated cells. In contrast to the in vivo condition, secreted IgG derived from the PBMC-DENV culture was not DENV-specific. Lower ASC numbers were observed when inactivated viral particles or purified B cells were added to the cultures. The physical contact was essential between B cells and the remaining PBMCs for the DENV-mediated ASC response. Considering the evidence for the activation of the tryptophan metabolism detected in the serum of Dengue patients, we assessed its relevance in the DENV-mediated ASC differentiation. For this, tryptophan and its respective metabolites were quantified in the supernatants of cell cultures through mass spectrophotometry. Tryptophan depletion and kynurenine accumulation were found in the supernatants of PBMC-DENV cultures, which presented enhanced detection of indoleamine 2,3-dioxygenase 1 and 2 transcripts as compared to controls. In PBMC-DENV cultures, tryptophan and kynurenine levels strongly correlated to the respective ASC numbers, while the kynurenine levels were directly proportional to the secreted IgG titers. Contrastingly, PBMCs incubated with Zika or attenuated Yellow Fever viruses showed no correlation between their kynurenine concentrations and ASC numbers. Therefore, our data revealed the existence of distinct pathways for the DENV-mediated ASC differentiation and suggest the involvement of the tryptophan metabolism in this cellular process triggered by flavivirus infections.

Suction versus slow-pull for endoscopic ultrasound-guided fine-needle aspiration of pancreatic tumors: a prospective randomized trial.

BACKGROUND: Suction (S) is commonly used to improve cell acquisition during endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Slow-pull (SP) sampling is another technique that might procure good quality specimens with less bloodiness. We aimed to determine if SP improves the diagnostic yield of EUS-FNA of pancreatic masses. METHODS: Patients with pancreatic solid masses were randomized to four needle passes with both techniques in an alternate fashion. Sensitivity, specificity, positive, and negative predictive values were calculated. Cellularity and bloodiness of cytological samples were assessed and compared according to the technique. RESULTS: Sensitivity, specificity, and accuracy of suction vs. SP were 95.2% vs. 92.3%; 100% vs. 100; 95.7% vs. 93%, respectively. As to the association of methods, they were 95.6, 100 and 96%, respectively. Positive predictive values for S and SP were 100%. There was no difference in diagnostic yield between S and SP (p = 0.344). Cellularity of samples obtained with SP and Suction were equivalent in both smear evaluation (p = 0.119) and cell-block (0.980). Bloodiness of SP and suction techniques were similar as well. CONCLUSIONS: S and SP techniques provide equivalent sensitivity, specificity, and accuracy. Association of methods seems to improve diagnostic yield. Suction does not increase the bloodiness of samples compared to slow-pull.

Hydroquinone exposure alters the morphology of lymphoid organs in vaccinated C57Bl/6 mice.

The influenza is a common viral infection that can be fatal, especially in high-risk groups such as children, pregnant women, elderly, and immune-deficient individuals. Vaccination is the most efficient approach to prevent the spreading of viral infection and promote individual and public health. In contrast, exposure to environmental pollutants such as cigarette smoke reduces the efficacy of vaccination. We investigated whether chronic exposure to hydroquinone (HQ), the most abundant compound of the tobacco particulate phase, could impair the adaptive immune responses elicited by influenza vaccination. For this, adult male C57BL/6 mice were daily exposed to either nebulized HQ or PBS for 1 h for a total of eight weeks. At weeks 6 and 8, the mice were primed and boosted with the trivalent influenza vaccine via IM respectively. Although the HQ exposure did not alter the body weight of the mice and the biochemical and hematological parameters, the pollutant increased the oxidative stress in splenocytes of immunized animals, modified the morphology of spleen follicles, and augmented the size of their lymph nodes. The lymphoid organs of HQ-exposed mice presented a similar number of vaccine-specific IgG-secreting cells, titers of vaccine-specific total IgG, and respective subclasses. Transcriptome studies with HQ, benzene, or cigarette smoke exposure were also analyzed. The genes up-regulated upon pollutant exposure were associated with neutrophil migration and were shown to be co-expressed with antibody-secreting cell genes. Therefore, these findings suggest that HQ exposure may trigger an immune-compensatory mechanism that enhances the humoral responses induced by influenza vaccination.

Methods for predicting vaccine immunogenicity and reactogenicity.

Subjects receiving the same vaccine often show different levels of immune responses and some may even present adverse side effects to the vaccine. Systems vaccinology can combine omics data and machine learning techniques to obtain highly predictive signatures of vaccine immunogenicity and reactogenicity. Currently, several machine learning methods are already available to researchers with no background in bioinformatics. Here we described the four main steps to discover markers of vaccine immunogenicity and reactogenicity: (1) Preparing the data; (2) Selecting the vaccinees and relevant genes; (3) Choosing the algorithm; (4) Blind testing your model. With the increasing number of Systems Vaccinology datasets being generated, we expect that the accuracy and robustness of signatures of vaccine reactogenicity and immunogenicity will significantly improve.

Hydroquinone exposure alters the morphology of lymphoid organs in vaccinated C57Bl/6 mice

The influenza is a common viral infection that can be fatal, especially in high-risk groups such as children, pregnant women, elderly, and immune-deficient individuals. Vaccination is the most efficient approach to prevent the spreading of viral infection and promote individual and public health. In contrast, exposure to environmental pollutants such as cigarette smoke reduces the efficacy of vaccination. We investigated whether chronic exposure to hydroquinone (HQ), the most abundant compound of the tobacco particulate phase, could impair the adaptive immune responses elicited by influenza vaccination. For this, adult male C57BL/6 mice were daily exposed to either nebulized HQ or PBS for 1 h for a total of eight weeks. At weeks 6 and 8, the mice were primed and boosted with the trivalent influenza vaccine via IM respectively. Although the HQ exposure did not alter the body weight of the mice and the biochemical and hematological parameters, the pollutant increased the oxidative stress in splenocytes of immunized animals, modified the morphology of spleen follicles, and augmented the size of their lymph nodes. The lymphoid organs of HQ-exposed mice presented a similar number of vaccine-specific IgG-secreting cells, titers of vaccine-specific total IgG, and respective subclasses. Transcriptome studies with HQ, benzene, or cigarette smoke exposure were also analyzed. The genes up-regulated upon pollutant exposure were associated with neutrophil migration and were shown to be co-expressed with antibody-secreting cell genes. Therefore, these findings suggest that HQ exposure may trigger an immune-compensatory mechanism that enhances the humoral responses induced by influenza vaccination.