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1.
PLoS One ; 17(5): e0267653, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35522661

RESUMO

Dengue is caused by an arbovirus that belongs to the Flaviviridae family and there are four distinct, but close related, circulating serotypes. Dengue disease is of great importance for global public health, with vaccination being its main prophylactic measure. However, there is a paucity of biological models for evaluating tetravalent dengue vaccines. The aim of this study was to evaluate the susceptibility of human cell lines HEK293T and THP-1 to a commercial dengue vaccine and test the feasibility of this approach in the development of a potency assay with human cell lines, as a methodological alternative to the golden standard potency assay with VERO cells. In this context, we used a batch of the commercial vaccine Dengvaxia® (CYD-TDV) for the infection tests. We evaluated the presence of the vaccine virus in THP-1 cells, differentiated into macrophages (dTHP-1), and in HEK293T by confocal microscopy, using 4G2 pan-flavivirus antibody. Vaccine infectivity and potency were determined by immunocolorimetric assay using monoclonal antibodies specific for each serotype. The results indicated that the human strain HEK293T was responsive to the tetravalent vaccine, as shown by the presence of virus particles in the cell cytoplasm in a pattern similar to the one observed with VERO cells. Moreover, it was possible to determine the infectivity and potency values of each vaccine virus serotype in the HEK293T, with serotype 4 prevailing over the others. Thus, the human cell line HEK293T provides a potential candidate to be used in assays to determine potency and identity of tetravalent dengue vaccines.


Assuntos
Vacinas contra Dengue , Dengue , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Chlorocebus aethiops , Dengue/prevenção & controle , Estudos de Viabilidade , Células HEK293 , Humanos , Vacinas Atenuadas , Vacinas Combinadas , Células Vero
2.
Front Immunol ; 13: 869757, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35529859

RESUMO

Malaria remains one of the world's most prevalent infectious diseases. Several vaccination strategies currently under investigation aim at hampering the development of the Plasmodium parasite during the clinically silent liver stage of its life cycle in the mammalian host, preventing the subsequent disease-associated blood stage of infection. Immunization with radiation-attenuated sporozoites (RAS), the liver-infecting parasite forms, can induce sterile protection against malaria. However, the efficacy of vaccine candidates in malaria-naïve individuals in high-income countries is frequently higher than that found in populations where malaria is endemic. Malnutrition has been associated with immune dysfunction and with a delay or impairment of the immune response to some vaccines. Since vaccine efficacy depends on the generation of competent immune responses, and malaria-endemic regions are often associated with malnutrition, we hypothesized that an inadequate host nutritional status, specifically resulting from a reduction in dietary protein, could impact on the establishment of an efficient anti-malarial immune response. We developed a model of RAS immunization under low protein diet to investigate the impact of a reduced host protein intake on the immunogenicity and protective efficacy of this vaccine. Our analysis of the circulating and tissue-associated immune compartments revealed that a reduction in dietary protein intake during immunization resulted in a decrease in the frequency of circulating CD4+ T cells and of hepatic NK cells. Nevertheless, the profile of CD8+ T cells in the blood, liver and spleen was robust and minimally affected by the dietary protein content during RAS immunization, as assessed by supervised and in-depth unsupervised X-shift clustering analysis. Although mice immunized under low protein diet presented higher parasite liver load upon challenge than those immunized under adequate protein intake, the two groups displayed similar levels of protection from disease. Overall, our data indicate that dietary protein reduction may have minimal impact on the immunogenicity and efficacy of RAS-based malaria vaccination. Importantly, this experimental model can be extended to assess the impact of other nutrient imbalances and immunization strategies, towards the refinement of future translational interventions that improve vaccine efficacy in malnourished individuals.


Assuntos
Vacinas Antimaláricas , Malária , Desnutrição , Animais , Dieta com Restrição de Proteínas , Proteínas na Dieta , Mamíferos , Camundongos , Esporozoítos , Vacinação/métodos , Vacinas Atenuadas
3.
Front Immunol ; 13: 874871, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35529865

RESUMO

Brucellosis is an important zoonotic disease that causes great economic losses. Vaccine immunisation is the main strategy for the prevention and control of brucellosis. Although live attenuated vaccines play important roles in the prevention of this disease, they also have several limitations, such as residual virulence and difficulty in the differentiation of immunisation and infection. We developed and evaluated a new bacterial ghost vaccine of Brucella abortus A19 by a new double inactivation method. The results showed that the bacterial ghost vaccine of Brucella represents a more safe and efficient vaccine for brucellosis. We further characterised the antigenic components and signatures of the vaccine candidate A19BG. Here, we utilised a mass spectrometry-based label-free relative quantitative proteomics approach to investigate the global proteomics changes in A19BGs compared to its parental A19. The proteomic analysis identified 2014 proteins, 1116 of which were differentially expressed compared with those in A19. The common immunological proteins of OMPs (Bcsp31, Omp25, Omp10, Omp19, Omp28, and Omp2a), HSPs (DnaK, GroS, and GroL), and SodC were enriched in the proteome of A19BG. By protein micro array-based antibody profiling, significant differences were observed between A19BG and A19 immune response, and a number of signature immunogenic proteins were identified. Two of these proteins, the BMEII0032 and BMEI0892 proteins were significantly different (P < 0.01) in distinguishing between A19 and A19BG immune sera and were identified as differential diagnostic antigens for the A19BG vaccine candidate. In conclusion, using comparative proteomics and antibody profiling, protein components and signature antigens were identified for the ghost vaccine candidate A19BG, which are valuable for further developing the vaccine and its monitoring assays.


Assuntos
Vacina contra Brucelose , Brucelose , Vacinas Bacterianas , Brucella abortus , Brucelose/microbiologia , Brucelose/prevenção & controle , Humanos , Proteômica , Vacinas Atenuadas
4.
Trop Biomed ; 39(1): 47-54, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35507924

RESUMO

There are many infectious animal diseases in T urkey and generally, vaccination is the primarly control strategy to combat them. However, it is difficult to apply all vaccines in a definite period in the field due to limitations of the labor and finance. Rapid vaccination and effective use of labor can be possible with the help of simultaneous vaccine administrations. The study aims to show the effects of simultaneous foot-and-mouth disease (FMD), peste des petits ruminants (PPR), sheep pox and goat pox (SGP), and bluetongue (BT) vaccine administration on the antibody response of sheep. For this aim, 30 sheep were divided into one experiment and 5 control groups. Blood samples were collected in each group at 0, 30 and 60 days post-vaccination (DPV). Immune response was measured with virus neutralization test (VNT) and, liquid phase blocking ELISA (LPBE) for FMDV; VNT for BTV and PPR. A live virus challenge study was performed to determine the immune response of SGP vaccine. As a result, antibody titers for each vaccine agent decreased on 60 DPV with the simultaneous vaccination except FMD. The difference between means of antibody titer decrease with single and simultaneous vaccinations is significant especially for BTV and PPR vaccines at 60DPV (p<0.05). Briefly, this decreasing immune response of three live vaccines can be explained with the development of the interference, administration of these vaccines from the same injection site, the effect of cytokines, especially IL-10 effect of SGP vaccine. It was concluded that four vaccines can not be used simultaneously in sheep.


Assuntos
Bluetongue , Febre Aftosa , Doenças das Cabras , Peste dos Pequenos Ruminantes , Vírus da Peste dos Pequenos Ruminantes , Doenças dos Ovinos , Animais , Anticorpos Antivirais , Formação de Anticorpos , Bluetongue/prevenção & controle , Febre Aftosa/prevenção & controle , Doenças das Cabras/prevenção & controle , Cabras , Peste dos Pequenos Ruminantes/prevenção & controle , Ovinos , Doenças dos Ovinos/prevenção & controle , Vacinação/veterinária , Vacinas Atenuadas
5.
Vopr Virusol ; 67(2): 133-141, 2022 May 05.
Artigo em Russo | MEDLINE | ID: mdl-35521986

RESUMO

INTRODUCTION: Rubella is currently an infection controlled by specific prophylaxis. Not only the right vaccine prophylaxis strategy and tactics, but also the use of effective and safe vaccine preparations is crucial for the elimination of this disease.The aim of the investigation was to study the morphological and pathogenetic patterns of changes developing in the central nervous system (CNS) and internal organs of monkeys (Haplorhini) during intracerebral inoculation with 2 strains of rubella virus (Matonaviridae: Rubivirus: Rubella virus) (RV): highly attenuated Orlov-B, and low attenuated Orlov-14. MATERIAL AND METHODS: In the experiments, seronegative rhesus macaque monkeys (Macaca mulatta) weighing 3.3-5.1 kg (n = 7) were used. Neurovirulence of the strains was determined by a complex of clinical, pathomorphological, and virological methods. RESULTS AND DISCUSSION: It was found that during attenuation, the Orlov-B strain lost the ability to replicate in CNS cells and induce moderate/expressed specific changes in them, as well as to overcome the blood-brain barrier and cause the damage of sensitive organs and tissues. This fact indicates a low level of residual neurovirulence of the vaccine strain. CONCLUSION: The results obtained in this study regarding the clinical symptoms of CNS lesions and the nature of the pathological process in its tissues in experimental animals can be significant for the improvement of safety control of live rubella vaccines. These data indicate that the Orlov-B strain can be considered as a candidate strain for further study on the development of a rubella vaccine based on the domestic vaccine strain.


Assuntos
Vírus da Rubéola , Rubéola (Sarampo Alemão) , Animais , Macaca mulatta , Vacina contra Rubéola , Rubivirus , Vacinas Atenuadas
6.
Front Immunol ; 13: 845680, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432301

RESUMO

Cyclic dimeric guanosine monophosphate (c-di-GMP) is a bacterial second messenger with immunomodulatory activities in mice, suggesting potential applications as a vaccine immunopotentiator or therapeutic agent. In this study, we evaluated the efficacy of c-di-GMP as an immunopotentiator for pseudorabies virus (PRV) inactivated vaccine in a murine model. We found that c-di-GMP improved the humoral and cellular immune responses induced by PRV inactivated vaccine and its effects on immunity reached the level comparable to that of a live attenuated vaccine. Furthermore, c-di-GMP enhanced the murine antibody response against the viral glycoprotein gB up to 120 days after immunization. The c-di-GMP-adjuvanted PRV inactivated vaccine induced long-term humoral immunity by promoting a potent T follicular helper cell response, which is known to directly control the magnitude of the germinal center B cell response. Furthermore, the c-di-GMP enhanced the response of bone marrow plasma cells and upregulated the expression of Bcl-2 and Mcl-1, which have been identified as anti-apoptotic regulatory genes of germinal center and memory B cells. Our findings open a new avenue for improving the immune efficacy of PRV inactivated vaccines.


Assuntos
Herpesvirus Suídeo 1 , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Antivirais , GMP Cíclico/análogos & derivados , Imunidade Humoral , Camundongos , Vacinas Atenuadas , Vacinas de Produtos Inativados
7.
Sci Rep ; 12(1): 6641, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35477976

RESUMO

Endogenous retroviruses (ERVs) are retroviral sequences present in the host genomes. Although most ERVs are inactivated, some are produced as replication-competent viruses from host cells. We previously reported that several live-attenuated vaccines for companion animals prepared using the Crandell-Rees feline kidney (CRFK) cell line were contaminated with a replication-competent feline ERV termed RD-114 virus. We also found that the infectious RD-114 virus can be generated by recombination between multiple RD-114 virus-related proviruses (RDRSs) in CRFK cells. In this study, we knocked out RDRS env genes using the genome-editing tool TAL Effector Nuclease (TALEN) to reduce the risk of contamination by infectious ERVs in vaccine products. As a result, we succeeded in establishing RDRS knockout CRFK cells (RDKO_CRFK cells) that do not produce infectious RD-114 virus. The growth kinetics of feline herpesvirus type 1, calicivirus, and panleukopenia virus in RDKO_CRFK cells differed from those in parental cells, but all of them showed high titers exceeding 107 TCID50/mL. Infectious RD-114 virus was undetectable in the viral stocks propagated in RDKO_CRFK cells. This study suggested that RDRS env gene-knockout CRFK cells will be useful as a cell line for the manufacture of live-attenuated vaccines or biological substances with no risk of contamination with infectious ERV.


Assuntos
Retrovirus Endógenos , Animais , Gatos , Retrovirus Endógenos/genética , Rim , Tecnologia , Nucleases dos Efetores Semelhantes a Ativadores de Transcrição/genética , Efetores Semelhantes a Ativadores de Transcrição/genética , Vacinas Atenuadas
8.
Vaccine ; 40(19): 2723-2732, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35367071

RESUMO

Control of swine influenza A virus (swIAV) in North America and Europe is complicated because multiple antigenically distinct swIAV strains co-circulate in the field, and no vaccine is available that can provide broad cross-protection against all these swIAVs. In 2017, the first live attenuated influenza vaccine (LAIV) for swine was licensed in the US. The non-structural protein 1 (NS1)-truncated cluster I H3N2 strain A/swine/Texas/4199-2/98 NS1del126 (TX98 LAIV) in this vaccine provides partial cross-protection against heterologous North American cluster II and IV H3N2 swIAV strains. Its efficacy against European or more recent North American H3N2 lineages remains to be investigated. In this study, we evaluated the level of cross-protection against heterologous IAVs representative of the major H3N2 swIAV lineages in Europe and North America. TX98 LAIV prevented both nasal shedding and replication in the lungs of a North American cluster IV H3N2 swIAV for 2/4 pigs, prevented considerable nasal shedding of a North American novel human-like H3N2 swIAV for 2/4 pigs, and reduced replication of a European H3N2 swIAV in the lower respiratory tract to minimal titers for 1/3 pigs. Although TX98 LAIV elicited neutralizing antibodies against the homologous virus in serum and to a lesser extent in nose and lungs, no significant cross-reactive antibody titers against the heterologous swIAVs were detected. Partial cross-protection therefore likely relies on cellular and mucosal immune responses against conserved parts of the swIAV proteins. Since TX98 LAIV can offer partial protection against a broad range of H3N2 swIAVs, it might be a suitable priming vaccine for use in a heterologous prime-boost vaccination strategy.


Assuntos
Vírus da Influenza A , Vacinas contra Influenza , Infecções por Orthomyxoviridae , Doenças dos Suínos , Animais , Anticorpos Antivirais , Vírus da Influenza A Subtipo H3N2 , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/veterinária , Suínos , Texas , Vacinas Atenuadas
9.
Washington, D.C.; OPAS; 2022-04-28.
em Português | PAHO-IRIS | ID: phr-55946

RESUMO

Um dos componentes essenciais de um sistema de vacinação seguro é a vigilância de eventos supostamente atribuíveis à vacinação ou imunização (ESAVI). Por meio dessa vigilância, busca-se detectar precocemente qualquer evento adverso que ocorra após a vacinação, a fim de controlar e classificar os riscos relacionados à vacina ou aos processos de fabricação, transporte, armazenamento e aplicação, bem como a qualquer situação inerente à pessoa vacinada ou para afastar a relação de tais eventos com a vacina. Este manual foi adaptado para a Região das Américas a partir do Manual Global para Vigilância de Eventos Adversos Pós-Vacinação, publicado pela Organização Mundial da Saúde em 2014. Ele fornece uma revisão técnica abrangente de todos os processos e procedimentos para implementar e operar sistemas de alta qualidade para a vigilância de ESAVI. Reúne a experiência de vários especialistas em segurança de vacinas da Região e do mundo, especialistas de programas nacionais de imunização, autoridades reguladoras nacionais e outras instituições que desenvolveram conhecimento relevante para a vigilância desses eventos. Espera-se que este documento sirva de guia para que os responsáveis pelos programas nacionais de imunização, os diretores de farmacovigilância das autoridades reguladoras nacionais e as demais instituições responsáveis pelo monitoramento da segurança das vacinas tenham ferramentas que facilitem sua tarefa e permitam a aplicação de normas internacionais em temas como detecção e investigação de ESAVI, análise de causalidade, gerenciamento de dados e comunicação de risco, entre outros.


Assuntos
Imunização , Programas de Imunização , Imunidade Coletiva , Vacinação em Massa , Imunização Passiva , Vacinas , Vacinas Atenuadas , Adjuvantes Imunológicos , Antibacterianos
10.
Washington, D.C.; PAHO; 2022-04-28.
em Inglês | PAHO-IRIS | ID: phr-55945

RESUMO

One of the essential components of the safe vaccination system is the surveillance of events supposedly attributable to vaccination or immunization (ESAVI). This surveillance is aimed at early detection of any adverse events that may occur following immunization, in order to monitor and classify risks related to a vaccine, the manufacturing process, transportation, storage, administration, and any preexisting condition in the vaccinated person, and to rule out an association between the event and the vaccine. This manual has been adapted for the Region of the Americas from the Global Manual on Surveillance of Adverse Events Following Immunization, published by the World Health Organization in 2014. It provides a comprehensive technical review of all processes and procedures for applying and implementing high-quality ESAVI surveillance systems. It brings together the expertise of vaccine safety specialists from the Region and from around the world, experts from national immunization programs, national regulatory bodies, and other institutions that have developed relevant knowledge on surveillance of these events. It is hoped that this document will serve as a guide to provide national immunization program managers, pharmacovigilance officers of national regulatory authorities, and other institutions responsible for monitoring vaccine safety with tools to facilitate their task, enabling them to apply international standards to issues such as event detection, event investigation, causality assessment, management of ESAVI data, and risk communication.


Assuntos
Imunização , Programas de Imunização , Imunidade Coletiva , Vacinação em Massa , Imunização Passiva , Vacinas , Vacinas Atenuadas , Adjuvantes Imunológicos , Antibacterianos
11.
Viruses ; 14(3)2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-35336854

RESUMO

A live attenuated duck Tembusu virus (TMUV) vaccine FX2010-180P (180P) was successfully utilized to prevent TMUV infections in ducks in China. Compared with wild-type TMUV, 180P was highly attenuated and lost transmissibility in ducks. However, the mechanism of the attenuation of 180P remains poorly understood. To explore the key molecular basis of attenuation, chimeric and site mutant viruses in the background of the wild-type TMUV-FX2010 (FX) strain were rescued, and the replication, tissue tropism, and transmissibility were characterized in ducks. The results show that the envelope (E) protein was responsible for attenuation and loss of transmission in ducks. Further studies showed that a D120N amino acid mutation located in domain II of the E protein was responsible for the attenuation and transmissibility loss of 180P in ducks. The D120N substitution resulted in an extra high-mannose type N-linked glycosylation (NLG) in the E protein of 180P compared with the wild-type TMUV, which might restrict the tissue tropism and transmissibility of TMUV in ducks. Our findings elucidate that N120 in the E protein is a key molecular basis of TMUV attenuation in ducks and provide new insight into the role of NLG in TMUV tissue tropism and transmissibility.


Assuntos
Infecções por Flavivirus , Flavivirus , Doenças das Aves Domésticas , Animais , Linhagem Celular , Patos , Flavivirus/genética , Infecções por Flavivirus/prevenção & controle , Infecções por Flavivirus/veterinária , Mutação , Vacinas Atenuadas
12.
Travel Med Infect Dis ; 47: 102289, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35227862

RESUMO

BACKGROUND: Yellow fever (YF) vaccination is the single most important preventative measure against YF infection, however the live attenuated vaccine has associated serious adverse events. All YF vaccinations in England, Wales and Northern Ireland (EWNI) are administered in YF Vaccination Centres and comply with National Travel Health Network and Centre (NaTHNaC) Conditions of Designation and Code of Practice, including reporting of vaccine incidents to NaTHNaC. In this study we evaluated the number and type of YF vaccine incidents in EWNI to identify areas for improvement. METHODS: NaTHNaC's telephone advice line database was retrospectively searched from 1st January 2016 to 31st December 2018 for YF vaccine incidents. Calls were categorised and analysed according to incident type. RESULTS: Seventy-eight YF vaccine incidents were reported from a total of 17250 calls. The commonest incident was incorrect timing of measles, mumps and rubella vaccine in relation to YF vaccine, where the recommended 28-day interval was not observed (n = 21). Other incidents included accidental partial vaccination (n = 11), inappropriate vaccination (n = 5) and invalid vaccination due to expiry or cold chain breach (n = 4). Inadvertent vaccination in contraindicated individuals occurred in two travellers with thymectomies (resulting in one death), and five immunocompromised travellers. CONCLUSIONS: YF vaccine incidents represent a small proportion of total calls. Similar incidents likely occur with other vaccines, but YF vaccine incidents are of particular concern; whilst most incidents were not harmful, vaccination in contraindicated individuals resulted in one death. These findings helped to inform new guidance and update training for staff in YF vaccination centres.


Assuntos
Vacina contra Febre Amarela , Febre Amarela , Humanos , Estudos Retrospectivos , Reino Unido , Vacinação/efeitos adversos , Vacinação/métodos , Vacinas Atenuadas , Febre Amarela/epidemiologia , Febre Amarela/prevenção & controle
13.
Front Immunol ; 13: 851028, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242146

RESUMO

Ionizing radiation (UV, X-ray and É£) administered at an appropriate dose to pathogenic organisms can prevent replication while preserving metabolic activity. We have established the GMP process for attenuation by ionizing radiation of the Plasmodium falciparum (Pf) sporozoites (SPZ) in Sanaria® PfSPZ Vaccine, a protective vaccine against malaria. Mosquitoes raised and infected aseptically with Pf were transferred into infected mosquito transport containers (IMTC) and É£-irradiated using a 60Co source. PfSPZ were then extracted, purified, vialed, and cryopreserved. To establish the appropriate radiation conditions, the irradiation field inside the IMTCs was mapped using radiochromic film and alanine transfer dosimeters. Dosimeters were irradiated for times calculated to provide 120-170 Gy at the minimum dose location inside the IMTC and regression analysis was used to determine the time required to achieve a lower 95% confidence interval for 150 Gy. A formula incorporating the half-life of 60Co was then used to construct tables of irradiation times for each calendar day. From the mapping studies, formulae were derived to estimate the minimum and maximum doses of irradiation received inside the IMTC from a reference dosimeter mounted on the outside wall. For PfSPZ Vaccine manufacture a dose of 150 Gy was targeted for each irradiation event, a dose known to completely attenuate PfSPZ. The reference dosimeters were processed by the National Institute of Standards and Technology. There have been 587 irradiation events to produce PfSPZ Vaccine during 13 years which generated multiple lots released for pre-clinical studies and clinical trials. The estimated doses at the minimum dose location (mean 154.3 ± 1.77 Gy; range 150.0-159.3 Gy), and maximum dose location (mean 166.3 ± 3.65 Gy, range 155.7 to 175.3 Gy), in IMTCs were normally distributed. Overall dose uniformity was 1.078 ± 0.012. There was no siginifcant change in measured dose over 13 years. As of January 2022, 21 clinical trials of PfSPZ Vaccine have been conducted, with 1,740 volunteers aged 5 months to 61 years receiving 5,648 doses of PfSPZ Vaccine totalling >5.3 billion PfSPZ administered. There have been no breakthrough infections, confirming the consistency and robustness of the radiation attenuation process.


Assuntos
Culicidae , Vacinas Antimaláricas , Malária Falciparum , Malária , Animais , Humanos , Malária Falciparum/prevenção & controle , Plasmodium falciparum , Esporozoítos , Vacinas Atenuadas , Vacinologia
14.
Vaccine ; 40(18): 2580-2587, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35341645

RESUMO

BACKGROUND: Oral rotavirus vaccine efficacy is lower in low- and middle-income countries (LMICs) than in high-income countries. The degree to which antibiotic use impacts rotavirus vaccine immunogenicity in LMICs is unknown. Using data from a multisite prospective birth cohort study of malnutrition and enteric disease, MAL-ED, we examined the effect of early life antibiotic use on the immune response to rotavirus vaccine. METHODS: We assessed whether antibiotic use from birth up to 7 days following rotavirus vaccine series completion was associated with rotavirus seropositivity at 7 months of age in Brazil, Peru, and South Africa using a modified Poisson regression. We then used parametric g-computation to estimate the impact of hypothetical interventions that treated all children and alternatively prevented inappropriate antibiotic treatments on seropositivity. RESULTS: Of 537 children, 178 (33%) received at least one antibiotic course during the exposure window. Probability of seropositivity was 40% higher among children who had at least one course of antibiotics compared with those with no antibiotic exposure (PR: 1.40, 95% CI: 1.04, 1.89). There was no significant difference by the number of antibiotic courses received or total duration of antibiotics. Treating all children with antibiotics would be associated with a 19% (95% CI: 18%, 21%) absolute increase in seropositivity at 7 months. In contrast, removing inappropriate antibiotics would result in a 4% absolute reduction (95% CI: -5%, -2%) in seropositivity. CONCLUSIONS: Early life antibiotic use was associated with increased seropositivity. However, a hypothetical intervention to remove inappropriate antibiotics would have little effect on overall seropositivity. Further investigation into the underlying mechanisms of antibiotic use on the infant gut microbiome and immune response are needed.


Assuntos
Gastroenterite , Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Antibacterianos/uso terapêutico , Anticorpos Antivirais , Criança , Estudos de Coortes , Gastroenterite/prevenção & controle , Humanos , Lactente , Estudos Prospectivos , Vacinas contra Rotavirus/uso terapêutico , Vacinas Atenuadas
15.
Vaccine ; 40(14): 2184-2190, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35232596

RESUMO

BACKGROUND: The introduction of rotavirus vaccines in national immunization programs has decreased mortality and hospitalizations due to diarrhea. GSK's live-attenuated, human rotavirus vaccine (HRV) is a 2-dose vaccine for oral administration. Following the detection of porcine circovirus type 1 (PCV-1) in HRV, a PCV-free (no detection of PCV-1 and PCV-2 according to the detection limits of tests used) HRV was developed. The immunogenicity, reactogenicity and safety of a liquid (liq) PCV-free HRV were assessed in two prior studies. The present study aimed to generate additional reactogenicity and safety data. METHODS: This phase III, observer-blind, randomized, controlled multi-country study enrolled healthy 6-12-week-old infants. Infants were randomized to receive 2 doses of either the liq PCV-free HRV (N = 677) or the lyophilized (lyo) HRV (N = 674) 1-2 months apart. Solicited adverse events (AEs) were recorded for 8 days after each dose, unsolicited AEs for 31 days and serious AEs (SAEs) from dose 1 until the end of the 6-month safety follow-up. RESULTS: The occurrence of solicited general AEs was comparable between the liq PCV-free HRV and the lyo HRV groups, with irritability/fussiness being the most frequently reported (74.9% [95% confidence interval: 71.4-78.1] and 72.1% [68.6-75.5]). Unsolicited AEs were reported for 29.7% (26.3-33.3) and 30.6% (27.1-34.2) of infants in the liq PCV-free HRV and the lyo HRV group. A total of 39 and 38 infants reported at least one SAE, respectively. The most common SAEs were upper respiratory tract (0.7% and 0.9%) and urinary tract infections (0.9% and 0.6%). One SAE (constipation) in the liq PCV-free HRV group was considered as potentially causally related to vaccination by the investigator. No deaths were reported. CONCLUSIONS: The study showed that the reactogenicity and safety profiles of the liq PCV-free HRV and the lyo HRV are similar. CLINICALTRIALS: gov identifier: NCT0395474.


Assuntos
Circovirus , Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Humanos , Lactente , Vacinação , Vacinas Atenuadas
16.
Viruses ; 14(3)2022 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-35336933

RESUMO

The disease yellow fever was prevented by two live attenuated vaccines, strains 17D and French neurotropic vaccine (FNV), derived by serial passage of wild-type (WT) strains Asibi and French Viscerotropic virus (FVV), respectively. Both 17D and FNV displayed decreased genetic diversity and resistance to the antiviral Ribavirin compared to their WT parental strains, which are thought to contribute to their attenuated phenotypes. Subsequent studies found that only a few passages of WT strain FVV in HeLa cells resulted in an attenuated virus. In the current study, the genome sequence of FVV following five passages in HeLa cells (FVV HeLa p5) was determined through Next Generation Sequencing (NGS) with the aim to investigate the molecular basis of viral attenuation. It was found that WT FVV and FVV HeLa p5 virus differed by five amino acid substitutions: E-D155A, E-K331R, E-I412V, NS2A-T105A, and NS4B-V98I. Surprisingly, the genetic diversity and Ribavirin resistance of the FVV HeLa p5 virus were not statistically different to WT parent FVV. These findings suggest that while FVV HeLa p5 is attenuated, this is not dependent on a high-fidelity replication complex, characterized by reduced genetic diversity or increased Ribavirin stability, as seen with FNV and 17D vaccines.


Assuntos
Febre Amarela , Vírus da Febre Amarela , Variação Genética , Células HeLa , Humanos , Ribavirina/farmacologia , Vacinas Atenuadas/genética , Vírus da Febre Amarela/genética
17.
Microb Pathog ; 165: 105463, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35240287

RESUMO

Mycoplasma pneumoniae (M. pneumoniae) is the causative agent of both upper and lower respiratory infections that can lead to pneumonia, extrapulmonary complications and devastating sequela. With the increasing rate of macrolide-resistant strains, the severe clinical consequence of refractory mycoplasma pneumonia in children health calls for the need of vaccine research for this pathogen. In this report, the immunomodulatory effectiveness of a live attenuated M. pneumoniae vaccine was evaluated. The vaccine strain was a mutant strain of M. pneumoniae, MUT129, obtained after multiple passages of M129 strain in PPLO broth. The SNP/InDel detection results showed that mutations were present in genes encoding the adhesion organelle-associated proteins and lipoproteins of M. pneumoniae MUT129. Upon intranasal challenge of BALB/c mice with 1 × 107 CFU of MUT129, there were very small amount of Mycoplasma antigens and almost no M. pneumoniae present in the lung tissues of BALB/c mice. Besides, there was almost no inflammatory cell infiltration in the lung tissue. Results of the M. pneumoniae challenge study showed that mice immunized with MUT129 presented with less inflammation, lower detectable number of M. pneumoniae in the lungs when compared with the unimmunized mice. These results indicated that the live attenuated vaccine can efficiently prevent the proliferation of M. pneumonia in the lungs, reduce but not completely prevent the pulmonary inflammatory response.


Assuntos
Mycoplasma pneumoniae , Pneumonia por Mycoplasma , Animais , Pulmão , Macrolídeos , Camundongos , Camundongos Endogâmicos BALB C , Mycoplasma pneumoniae/genética , Pneumonia por Mycoplasma/prevenção & controle , Vacinas Atenuadas/genética
18.
PLoS One ; 17(3): e0259807, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35275912

RESUMO

Francisella tularensis is the etiologic agent of tularemia and a Tier I Select Agent. Subspecies tularensis (Type A) is the most virulent of the four subspecies and inhalation of as few as 10 cells can cause severe disease in humans. Due to its niche as a facultative intracellular pathogen, a successful tularemia vaccine must induce a robust cellular immune response, which is best achieved by a live, attenuated strain. F. tularensis strains lacking lipopolysaccharide (LPS) O-antigen are highly attenuated, but do not persist in the host long enough to induce protective immunity. Increasing the persistence of an O-antigen mutant may help stimulate protective immunity. Alginate encapsulation is frequently used with probiotics to increase persistence of bacteria within the gastrointestinal system, and was used to encapsulate the highly attenuated LVS O-antigen mutant WbtIG191V. Encapsulation with alginate followed by a poly-L-lysine/alginate coating increased survival of WbtIG191V in complement-active serum. In addition, BALB/c mice immunized intraperitoneally with encapsulated WbtIG191V combined with purified LPS survived longer than mock-immunized mice following intranasal challenge. Alginate encapsulation of the bacteria also increased antibody titers compared to non-encapsulated bacteria. These data suggest that alginate encapsulation provides a slow-release vehicle for bacterial deposits, as evidenced by the increased antibody titer and increased persistence in serum compared to freely suspended cells. Survival of mice against high-dose intranasal challenge with the LVS wildtype was similar between mice immunized within alginate capsules or with LVS, possibly due to the low number of animals used, but bacterial loads in the liver and spleen were the lowest in mice immunized with WbtIG191V and LPS in beads. However, an analysis of the immune response of surviving mice indicated that those vaccinated with the alginate vehicle upregulated cell-mediated immune pathways to a lesser extent than LVS-vaccinated mice. In summary, this vehicle, as formulated, may be more effective for pathogens that require predominately antibody-mediated immunity.


Assuntos
Francisella tularensis , Tularemia , Alginatos , Animais , Vacinas Bacterianas , Lipopolissacarídeos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Antígenos O/genética , Tularemia/microbiologia , Vacinas Atenuadas
19.
Virulence ; 13(1): 558-568, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35266442

RESUMO

Severe influenza complications are often caused by Streptococcus pneumoniae infection, which presents the most common cause of community-acquired pneumonia. We evaluated in a mouse model an associated virus-bacterial vaccine based on seasonal live influenza vaccines (LAIV) and S. pneumoniae chimeric protein comprising flagellin (PSPF). Intranasal immunization of mice with a complex of trivalent LAIV and PSPF caused an increased release of early cytokines in the lungs of mice. The immunogenicity of LAIV and PSPF in the associated vaccine composition was sometimes decreased compared to each vaccine preparation alone. Nevertheless, only vaccination of mice with LAIV+PSPF significantly reduced lethality and the bacterial load in the lungs in a model of post-influenza bacterial pneumonia. The study of the interactions of influenza viruses with bacterial peptides is important during the development of associated virus-bacterial vaccines intended for the prevention of severe post-influenza bacterial complications.


Assuntos
Vacinas contra Influenza , Influenza Humana , Infecções Pneumocócicas , Animais , Vacinas Bacterianas , Humanos , Influenza Humana/complicações , Influenza Humana/prevenção & controle , Camundongos , Peptídeos , Infecções Pneumocócicas/prevenção & controle , Vírus Satélites , Estações do Ano , Streptococcus pneumoniae , Vacinas Atenuadas
20.
Cell Rep Med ; 3(2): 100509, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35243417

RESUMO

The induction of broadly neutralizing antibodies (bNAbs) that target the hemagglutinin stalk domain is a promising strategy for the development of "universal" influenza virus vaccines. bNAbs can be boosted in adults by sequential exposure to heterosubtypic viruses through natural infection or vaccination. However, little is known about if or how bNAbs are induced by vaccination in more immunologically naive children. Here, we describe the impact of repeated seasonal influenza vaccination and vaccine type on induction of bNAbs against group 1 influenza viruses in a pediatric cohort enrolled in randomized controlled trials of seasonal influenza vaccination. Repeated seasonal vaccination results in significant boosting of a durable bNAb response. Boosting of serological bNAb titers is comparable within inactivated and live attenuated (LAIV) vaccinees and declines with age. These data provide insights into vaccine-elicited bNAb induction in children, which have important implications for the design of universal influenza vaccine modalities in this critical population.


Assuntos
Vacinas contra Influenza , Influenza Humana , Adulto , Anticorpos Amplamente Neutralizantes , Criança , Humanos , Influenza Humana/prevenção & controle , Estações do Ano , Vacinas Atenuadas
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