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1.
Arch Virol ; 165(8): 1777-1789, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32462286

RESUMO

Enterovirus D68 (EV-D68) infection may cause severe respiratory system manifestations in pediatric populations. Because of the lack of an effective preventive vaccine or specific therapeutic drug for this infection, the development of EV-D68-specific vaccines and antibodies has become increasingly important. In this study, we prepared an experimental EV-D68 vaccine inactivated by formaldehyde and found that the serum of rhesus macaques immunized with the inactivated EV-D68 vaccine exhibited potent neutralizing activity against EV-D68 virus in vitro. Subsequently, the antibody-mediated immune response of B cells elicited by the inactivated vaccine was evaluated in a rhesus monkey model. The binding activity, in vitro neutralization activity, and sequence properties of 28 paired antibodies from the rhesus macaques' EV-D68-specific single memory B cells were analyzed, and the EV-D68 VP1-specific antibody group was found to be the main constituent in vivo. Intriguingly, we also found a synergistic effect among the E15, E18 and E20 monoclonal antibodies from the rhesus macaques. Furthermore, we demonstrated the protective efficacy of maternal antibodies in suckling C57BL/6 mice. This study provides valuable information for the future development of EV-D68 vaccines.


Assuntos
Anticorpos Antivirais/imunologia , Linfócitos B/imunologia , Infecções por Enterovirus/imunologia , Enterovirus/imunologia , Macaca mulatta/imunologia , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Formação de Anticorpos/imunologia , Linfócitos B/virologia , Linhagem Celular , Chlorocebus aethiops/imunologia , Chlorocebus aethiops/virologia , Infecções por Enterovirus/virologia , Feminino , Células HEK293 , Humanos , Imunização/métodos , Macaca mulatta/virologia , Camundongos , Camundongos Endogâmicos C57BL , Infecções Respiratórias/imunologia , Infecções Respiratórias/virologia , Vacinação/métodos , Células Vero
2.
Vet Clin North Am Food Anim Pract ; 36(2): 461-472, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32451035

RESUMO

Vaccination of cattle against viral respiratory pathogens to minimize losses associated with bovine respiratory disease (BRD) is a common practice among producers and veterinarians. Three different calf populations in which BRD is most prevalent (recently weaned beef calves, preweaning beef calves, and young dairy calves) are the principal focus of morbidity and mortality prevention through vaccination; however, the evidence of vaccination efficacy is inconsistent in the literature. This review addresses the evidence of efficacy of vaccination in the prevention or reduction of naturally occurring and experimentally induced BRD in each calf group.


Assuntos
Complexo Respiratório Bovino/prevenção & controle , Vacinas Virais/administração & dosagem , Administração Intranasal/veterinária , Animais , Anticorpos Antivirais/imunologia , Complexo Respiratório Bovino/imunologia , Complexo Respiratório Bovino/microbiologia , Bovinos , Infusões Parenterais/veterinária , Vacinação/veterinária , Vacinas de Produtos Inativados/administração & dosagem , Vacinas Virais/imunologia
3.
Science ; 369(6499): 77-81, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-32376603

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas Virais , Animais , Anticorpos Neutralizantes/biossíntese , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/biossíntese , Anticorpos Antivirais/imunologia , Betacoronavirus/isolamento & purificação , Chlorocebus aethiops , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Relação Dose-Resposta Imunológica , Feminino , Imunogenicidade da Vacina , Imunoglobulina G/biossíntese , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Projetos Piloto , Pneumonia Viral/virologia , Ratos , Ratos Wistar , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Células Vero , Carga Viral , Vacinas Virais/administração & dosagem , Vacinas Virais/efeitos adversos , Vacinas Virais/imunologia
4.
Int J Nanomedicine ; 15: 2071-2083, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32273703

RESUMO

Background and Purpose: Adjuvant can reduce vaccine dosage and acquire better immune protection to the body, which helps to deal with the frequent outbreaks of influenza. Nanoemulsion adjuvants have been proved efficient, but the relationship between their key properties and the controlled release which greatly affects immune response is still unclear. The present work explores the role of factors such as particle size, the polydispersity index (PDI), stability and the safety of nanoemulsions by optimizing the water concentration, oil phase and modes of carrying, to explain the impact of those key factors above on adjuvant effect. Methods: Isopropyl myristate (IPM), white oil, soybean oil, and grape-kernel oil were chosen as the oil phase to explore their roles in emulsion characteristics and the adjuvant effect. ICR mice were immunized with an emulsion-inactivated H3N2 split influenza vaccine mixture, to compare the nanoemulsion's adjuvant with traditional aluminium hydroxide or complete Freund's adjuvant. Results: Particle size of all the nanoemulsion formed in our experiment ranged from 20 nm to 200 nm and did not change much when diluted with water, while the PDI decreased obviously, indicating that the particles tended to become more dispersive. Formulas with 80% or 85.6% water concentration showed significant higher HAI titer than aluminium hydroxide or complete Freund's adjuvant, and adsorption rather than capsule mode showed higher antigen delivery efficiency. As mentioned about oil phase, G (IPM), F (white oil), H (soybean oil), and I (grape-kernel oil) showed a decreasing trend in their adjuvant efficiency, and nanoemulsion G was the best adjuvant with smaller and uniform particle size. Conclusion: Emulsions with a smaller, uniform particle size had a better adjuvant effect, and the adsorption mode was generally more efficient than the capsule mode. The potential adjuvant order of the different oils was as follows: IPM > white oil > soybean oil > grape-kernel oil.


Assuntos
Adjuvantes Imunológicos/química , Sistemas de Liberação de Medicamentos/métodos , Emulsões/química , Vacinas contra Influenza/administração & dosagem , Nanoestruturas/química , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/farmacologia , Animais , Emulsões/administração & dosagem , Emulsões/farmacologia , Feminino , Vírus da Influenza A Subtipo H3N2 , Vacinas contra Influenza/imunologia , Camundongos Endogâmicos ICR , Óleos/química , Infecções por Orthomyxoviridae/prevenção & controle , Tamanho da Partícula , Óleo de Soja/química , Vacinas de Produtos Inativados , Água/química
7.
Arch Virol ; 165(6): 1299-1309, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32253616

RESUMO

Since late 2010, outbreaks of porcine epidemic diarrhea (PED) have been reported in the swine industry in China. A variant PEDV strain that differs from strain CV777 causes prevalent PEDV infections which commercial vaccines based on CV777 cannot provide complete protection. In this study, we designed a new vaccine based on the epidemic PEDV strain AH2012/12, adjuvanted with flagellin, a mucosal adjuvant that induces mucosal and systemic production of IgA. Three groups of pregnant sows were immunized twice, with a 14-day interval, with PEDV adjuvanted with flagellin, PEDV alone, or PBS before farrowing, and newborn piglets from each group were selected and challenged with PEDV. Immunization with this vaccine elicited high levels of IgG, IgA, and neutralizing antibodies in the serum and colostrum of sows, and newborn piglets were protected against PEDV while suckling. This study should guide the prevention and control strategies for PEDV infection, thereby reducing the losses associated with this virus.


Assuntos
Infecções por Coronavirus/veterinária , Flagelina/administração & dosagem , Vírus da Diarreia Epidêmica Suína/imunologia , Doenças dos Suínos/prevenção & controle , Vacinas Virais/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Animais Recém-Nascidos , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Linhagem Celular , Colostro/química , Infecções por Coronavirus/patologia , Infecções por Coronavirus/prevenção & controle , Feminino , Flagelina/imunologia , Imunização , Gravidez , Suínos , Doenças dos Suínos/patologia , Vacinas de Produtos Inativados/imunologia , Vacinas Virais/administração & dosagem
8.
PLoS Negl Trop Dis ; 14(3): e0007989, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32176695

RESUMO

After the large influx of Rohingya nationals (termed Forcibly Displaced Myanmar National; FDMN) from Rakhine State of Myanmar to Cox's Bazar in Bangladesh, it was apparent that outbreaks of cholera was very likely in this setting where people were living under adverse water and sanitation conditions. Large campaigns of oral cholera vaccine (OCV) were carried out as a preemptive measure to control cholera epidemics. The aim of the study was to evaluate the immune responses of healthy adults and children after administration of two doses of OCV at 14 days interval in FDMN population and compare with the response observed in Bangladeshi's vaccinated earlier. A cross-sectional immunogenicity study was conducted among FDMNs of three age cohort; in adults (18+years; n = 83), in older children (6-17 years; n = 63) and in younger children (1-5 years; n = 80). Capillary blood was collected at three time points to measure vibriocidal antibodies using either plasma or dried blood spot (DBS) specimens. There was a significant increase of responder frequency of vibriocidal antibody titer at day 14 in all groups for Vibrio cholerae O1 (Ogawa/Inaba: adults-64%/64%, older children-70%/89% and younger children-51%/75%). There was no overall difference of vibriocidal antibody titer between FDMN and Bangladeshi population at baseline (p = 0.07-0.08) and at day 14, day 28 in all age groups for both serotypes. The seroconversion rate and geometric mean titer (GMT) of either serotype were comparable using both plasma and DBS specimens. These results showed that OCV is capable of inducing robust immune responses in adults and children among the FDMN population which is comparable to that seen in Bangladeshi participants in different age groups or that reported from other cholera endemic countries. Our results also suggest that the displaced population were exposed to V. cholerae prior to seeking shelter in Bangladesh.


Assuntos
Vacinas contra Cólera/administração & dosagem , Vacinas contra Cólera/imunologia , Cólera/prevenção & controle , Refugiados , Administração Oral , Adolescente , Adulto , Anticorpos Antibacterianos/sangue , Bangladesh , Atividade Bactericida do Sangue , Criança , Pré-Escolar , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Esquemas de Imunização , Lactente , Masculino , Pessoa de Meia-Idade , Mianmar , Sorogrupo , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vibrio cholerae O1/classificação , Vibrio cholerae O1/imunologia , Adulto Jovem
9.
PLoS Negl Trop Dis ; 14(3): e0008142, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32210437

RESUMO

Human rabies, a neglected viral zoonosis, is preventable through domestic animals vaccination and post-exposure prophylaxis using inactivated rabies vaccines. During vaccine production, several mandatory in vivo quality control trials, such as potency, live virus, and safety, are responsible for the use of large numbers of laboratory animals. Over the years, global organizations encouraged the development of alternative methods to reduce, replace and refine the use of animals in the pharmaceutical industry. In this study we standardized an in vitro assay for determination of residual live virus combining viral isolation techniques with direct immunofluorescence detection and viral quantification by a molecular method. Standardization of viral recovery steps and quantification by RT-qPCR were performed and the combined method was shown to be 3 fold more sensitive than the in vivo assay. It was possible to identify viral suspensions cultures, which still had residual viable rabies virus particles, evidencing the importance to implement this method in quality control schemes of rabies vaccine production. In addition, this developed assay is more practical, inexpensive and less time consuming, producing results in just 4 days, which may allow greater agility in the internal quality control of the vaccine. The in vitro method may reduce 2/3rd of laboratory animals numbers used for this purpose, since it can be applied in the intermediate quality control of inactivated rabies vaccine production.


Assuntos
Vacinas Antirrábicas/normas , Vírus da Raiva/crescimento & desenvolvimento , Vírus da Raiva/isolamento & purificação , Tecnologia Farmacêutica/métodos , Tecnologia Farmacêutica/normas , Cultura de Vírus/métodos , Técnica Direta de Fluorescência para Anticorpo , Reação em Cadeia da Polimerase em Tempo Real , Vacinas de Produtos Inativados/normas
10.
Epidemiol Infect ; 148: e26, 2020 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-32046804

RESUMO

Studies in countries with high immunisation coverage suggest that the re-emergence of pertussis may be caused by a decreased duration of protection resulting from the replacement of whole-cell pertussis vaccine (WPV) with the acellular pertussis vaccine (APV). In China, WPV was introduced in 1978. The pertussis vaccination schedule advanced from an all-WPV schedule (1978-2007), to a mixed WPV/APV schedule (2008-2009), then to an all-APV schedule (2010-2016). Increases in the incidence of pertussis have been reported in recent years in Jinan and other cities in China. However, there have been few Chinese-population-based studies focused on the impact of schedule changes. We obtained annual pertussis incidences from 1956 to 2016 from the Jinan Notifiable Conditions Database. We used interrupted time series and segmented regression analyses to assess changes in pertussis incidence at the beginning of each year, and average annual changes during the intervention. Pertussis incidence decreased by 1.11 cases per 100 000 population (P = 0.743) immediately following WPV introduction in 1978 and declined significantly by 1.21 cases per 100 000 population per year (P < 0.0001) between 1978 and 2001. Immediately after APV replaced the fourth dose of WPV in 2008, the second and third doses in 2009, then replaced all four doses in 2010, pertussis incidence declined by 1.98, 1.98 and 1.08 cases per 100 000 population, respectively. However, the results were not statistically significant. There were significant increasing trends in pertussis incidence after APV replacements: 1.63, 1.77 and 1.78 cases/year in 2008-2016, 2009-2016 and 2010-2016, respectively. Our study shows that the impact of an all-WPV schedule may be less than the impacts of the sequential WPV/APV schedules. The short-term impact of APV was better than that of WPV; however, the duration of APV-induced protection was not ideal. The impact and duration of protective immunity resulting from APVs produced in China need further evaluation. Further research on the effectiveness of pertussis vaccination programme in Jinan, China is also necessary.


Assuntos
Esquemas de Imunização , Vacina contra Coqueluche/administração & dosagem , Vacina contra Coqueluche/imunologia , Coqueluche/epidemiologia , Coqueluche/prevenção & controle , Adolescente , Adulto , Criança , Pré-Escolar , China/epidemiologia , Cidades/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Análise de Séries Temporais Interrompida , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Vacinas Acelulares/administração & dosagem , Vacinas Acelulares/imunologia , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Adulto Jovem
11.
PLoS One ; 15(2): e0229279, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101582

RESUMO

There is concern that influenza vaccine effectiveness (VE) may be attenuated by passage in eggs during manufacture. We compared quadrivalent cell-culture vaccine with egg-based vaccines, most of which were trivalent, against influenza A and B during 2017-2018 when A(H3N2) and B/Yamagata (present only in quadrivalent vaccines) predominated. We retrospectively examined risk of PCR-confirmed influenza A and B in members of Kaiser Permanente Northern California aged 4-64 years. We estimated the relative VE (rVE) of cell-culture vaccine versus egg-based vaccines, and the absolute VE (aVE) of each vaccine comparing vaccinated to unvaccinated individuals. Analyses used Cox regression with a calendar timeline, stratified by birth year, and adjusted for demographics, co-morbidities and utilization. One-third (1,016,965/3,053,248) of the population was vaccinated; 932,545 (91.7% of vaccinees) received egg-based and 84,420 (8.3%) received cell-culture vaccines. The rVE against influenza A was 8.0% (95% CI: -10, 23); aVE was 31.7% (CI: 18.7, 42.6) for cell-culture and 20.1% (CI: 14.5, 25.4) for egg-based vaccines. The rVE against influenza B was 39.6% (CI: 27.9, 49.3); aVE was 40.9% (CI: 30, 50.1) for cell-culture and 9.7% (CI 3.5, 15.6) for egg-based trivalent vaccines. Inclusion of the B/Yamagata lineage in the quadrivalent cell-based vaccine provided better protection against influenza B but vaccine effectiveness against influenza A was low for both the cell-culture vaccine and the egg-based vaccines. Improving influenza vaccines requires ongoing comparative vaccine effectiveness monitoring.


Assuntos
Ovos , Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Vacinação/estatística & dados numéricos , Vacinas de Produtos Inativados/administração & dosagem , Adolescente , Adulto , California/epidemiologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Vírus da Influenza A/isolamento & purificação , Influenza Humana/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Estações do Ano , Fatores de Tempo , Adulto Jovem
12.
Medicine (Baltimore) ; 99(7): e19095, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049815

RESUMO

BACKGROUND: Influenza is a severe disease burden among all age groups. This study aimed to review the efficacy of inactivated influenza vaccines with MF59 adjuvant and non-adjuvanted inactivated influenza vaccines among all age groups against specific influenza vaccine strains. METHODS: Literature search of PubMed, Embase, Medline, OVID, and Cochrane Library Trials (CENTRAL) was implemented up to March 1, 2019. Homogeneity qualified studies were included forData were extracted such as study country location, demographic characteristics, and measure outcomes, and were analyzed by a random effect model and sensitivity analyses to identify heterogeneity. Risk of bias was evaluated using the Cochrane Risk of Bias Tool. RESULTS: We retrieved 1,021 publications and selected 31 studies for full review, including 17 trials for meta-analysis and 6 trials for qualitative synthesis. MF59-adjuvanted influenza vaccines demonstrated better immunogenicity against specific vaccine virus strains compared to non-adjuvanted influenza vaccine both in healthy adult group (RR = 2.10; 95% CI: 1.28-3.44) and the healthy aged (RR = 1.26; 95% CI: 1.10-1.44). CONCLUSION: The quality of evidence is moderate to high for seroconversion and seroprotection rates of influenza vaccine. MF59-adjuvanted influenza vaccines are superior to non-adjuvanted influenza vaccines to enhance immune responses of vaccination in healthy adults and older adults, and could be considered for routine use especially the monovalent prepandemic influenza vaccines.


Assuntos
Imunogenicidade da Vacina/efeitos dos fármacos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Esqualeno/imunologia , Adjuvantes Imunológicos/administração & dosagem , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Vacinas contra Influenza/administração & dosagem , Influenza Humana/imunologia , Influenza Humana/virologia , Masculino , Pessoa de Meia-Idade , Polissorbatos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Soroconversão/efeitos dos fármacos , Esqualeno/administração & dosagem , Vacinas de Produtos Inativados , Adulto Jovem
13.
Nat Med ; 26(2): 228-235, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32015557

RESUMO

Zika virus (ZIKV) has caused significant disease, with widespread cases of neurological pathology and congenital neurologic defects. Rapid vaccine development has led to a number of candidates capable of eliciting potent ZIKV-neutralizing antibodies (reviewed in refs. 1-3). Despite advances in vaccine development, it remains unclear how ZIKV vaccination affects immune responses in humans with prior flavivirus immunity. Here we show that a single-dose immunization of ZIKV purified inactivated vaccine (ZPIV)4-7 in a dengue virus (DENV)-experienced human elicited potent cross-neutralizing antibodies to both ZIKV and DENV. Using a unique ZIKV virion-based sorting strategy, we isolated and characterized multiple antibodies, including one termed MZ4, which targets a novel site of vulnerability centered on the Envelope (E) domain I/III linker region and protects mice from viremia and viral dissemination following ZIKV or DENV-2 challenge. These data demonstrate that Zika vaccination in a DENV-experienced individual can boost pre-existing flavivirus immunity and elicit protective responses against both ZIKV and DENV. ZPIV vaccination in Puerto Rican individuals with prior flavivirus experience yielded similar cross-neutralizing potency after a single vaccination, highlighting the potential benefit of ZIKV vaccination in flavivirus-endemic areas.


Assuntos
Dengue/imunologia , Doadores de Tecidos , Vacinas Virais/uso terapêutico , Infecção por Zika virus/imunologia , Infecção por Zika virus/prevenção & controle , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Chlorocebus aethiops , Reações Cruzadas , Vírus da Dengue , Mapeamento de Epitopos , Feminino , Flavivirus/metabolismo , Humanos , Imunoglobulina G/química , Concentração Inibidora 50 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Ligação Proteica , Domínios Proteicos , Vacinação , Vacinas de Produtos Inativados/uso terapêutico , Células Vero , Viremia , Zika virus
14.
Int J Infect Dis ; 92: 29-37, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31838217

RESUMO

OBJECTIVES: To analyse the immunogenicity and safety of inactivated subunit quadrivalent influenza vaccine (QIV) versus trivalent influenza vaccine (TIV) in children and adolescents 3-17 years of age. METHODS: In this phase III, multicentre, double-blind study, 1200 subjects were randomized to receive QIV (n=402), TIV with the B-strain of the Victoria lineage (n=404), or TIV with the B-strain of the Yamagata lineage (n=394). The primary objective was to demonstrate non-inferiority of QIV to TIV for immunogenicity against shared influenza strains, based on post-vaccination hemagglutinin inhibition (HI) titres. Secondary objectives were to show superiority of QIV to TIV for immunogenicity against alternate-lineage B-strains, and to further characterize the immune response by analysing virus neutralization and neuraminidase inhibition titres. Reactogenicity and safety were also compared post-vaccination. RESULTS: QIV elicited a non-inferior response for shared strains (upper limits of the 95% confidence intervals for the HI geometric mean ratios (GMRs) of TIV/QIV<1.5) and a superior response for alternate-lineage B-strains (HI GMRs of TIV/QIV<1.0; p<0.0001) versus TIV. Reporting rates of local and systemic adverse reactions were similar between vaccine arms. CONCLUSIONS: QIV had comparable immunogenicity to TIV for shared strains and superior immunogenicity to the alternate-lineage B-strains in TIV. Safety and tolerability profiles were comparable.


Assuntos
Imunogenicidade da Vacina , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Adolescente , Anticorpos Antivirais , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Vírus da Influenza B/imunologia , Vacinas contra Influenza/efeitos adversos , Masculino , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia
15.
Infect Immun ; 88(3)2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-31792078

RESUMO

To understand the role of major histocompatibility complex class I (MHC-I) and MHC-II in vaccine-mediated protection against Coxiella burnetii, we evaluated the protective efficacy of a formalin-inactivated C. burnetii Nine Mile phase I vaccine (PIV) in ß2-microglobulin-deficient (B2m KO) and MHC-II-deficient (MHC-II KO) mice. Vaccination reduced disease severity in wild-type (WT) and B2m KO mice but failed to reduce bacterial burden in MHC-II KO mice. This suggests that the MHC-II antigen presentation pathway is required for PIV-mediated protection against C. burnetii infection. MHC-I and MHC-II affect antibody isotype switching, since both PIV-vaccinated B2m KO and MHC-II KO mice produced less Coxiella-specific IgG than PIV-vaccinated WT mice. Interestingly, MHC-II and CD4 deficiencies were not equivalent in terms of splenomegaly and bacterial clearance. This demonstrates a partial role for CD4+ T cells while revealing MHC-II-restricted, CD4-independent mechanisms. Adoptive transfer of CD4+ T cells from PIV-vaccinated WT mice to naive CD4-deficient (CD4 KO) mice demonstrated that antigen-experienced CD4+ T cells are sufficient to generate protection. Conversely, transfer of naive CD4+ T cells to PIV-vaccinated CD4 KO mice exacerbates disease. Using Tbet-deficient (Tbet KO) mice, we showed a partial role for Th1 subset CD4+ T cells in vaccine protection. Furthermore, Th1-independent roles for Tbet were suggested by significant differences in disease between PIV-vaccinated Tbet KO and CD4 KO mice. Interferon gamma was shown to contribute to the host inflammatory response but not bacterial clearance. Collectively, these findings suggest that vaccine-induced protective immunity against a murine model of experimental Q fever requires MHC-II-restricted, CD4+ T cell-dependent and -independent mechanisms that can be exploited for a new-generation human Q fever vaccine.


Assuntos
Vacinas Bacterianas/imunologia , Linfócitos T CD4-Positivos/imunologia , Coxiella burnetii/imunologia , Antígenos de Histocompatibilidade Classe II/imunologia , Vacinação/métodos , Vacinas de Produtos Inativados/imunologia , Transferência Adotiva , Animais , Antígenos de Bactérias/imunologia , Antígenos CD4/metabolismo , Imunoglobulina G/metabolismo , Interferon gama/imunologia , Camundongos Endogâmicos C57BL
16.
Mol Immunol ; 118: 132-141, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31881424

RESUMO

Control of Infectious bursal disease virus (IBDV) in endemic countries has been based on early immunization of chicks using conventional live or inactivated vaccines that became not fully effectual and have biosafety concerns. This endeavor seeks generating a recombinant chimeric protein merging the projection domain (PD) of IBDV VP2 capsid with the fragment crystallizable (Fc) of avian IgY (FcIgY), in maize as a prospective poultry edible vaccine. The PD sequence was built on the basis of very virulent IBDV isolates circulating in Egypt. After optimization of codon-usage in maize, sequences of PD and FcIgY were effectively expressed in two elites of yellow maize via bombardment transformation in immature embryos. Chimeric protein amount in stable transgenic samples ranged from1.36% to 3.03% of the total soluble protein based on tissue age and maize cultivar. IBDV VP2 coding sequence was amplified from viral RNA, cloned, and expressed in E. coli. A group of Balb/C mice were hyper-immunized with purified recombinant VP2 protein for raising anti- recombinant VP2 antibodies (anti-rVP2 Ab). Proper expression in maize and immunoreactivity of the chimeric protein (PD-FcIgY) to chicken anti- IBDV and anti-rVP2 Ab were confirmed by both direct and indirect double antibody sandwich (DAS)-ELISAs as well as western blotting. Seeds of regenerated transgenic maize will be validated for chickens as edible vaccination in further studies.


Assuntos
Galinhas/imunologia , Imunoglobulinas/imunologia , Vírus da Doença Infecciosa da Bursa/imunologia , Vacinas de Plantas Comestíveis/imunologia , Sequência de Aminoácidos , Animais , Anticorpos Antivirais/imunologia , Infecções por Birnaviridae/imunologia , Proteínas do Capsídeo/imunologia , Egito , Escherichia coli/imunologia , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Doenças das Aves Domésticas/imunologia , Estudos Prospectivos , Proteínas Recombinantes/imunologia , Alinhamento de Sequência , Vacinação/métodos , Vacinas de Produtos Inativados/imunologia , Proteínas Estruturais Virais/imunologia , Vacinas Virais/imunologia , Zea mays
17.
Parasite Immunol ; 42(1): e12682, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31644820

RESUMO

A whole-killed malaria blood-stage vaccine (WKV) is promising in reducing the morbidity and mortality of malaria patients, but its efficacy needs to be improved. We found that the antimalarial drug chloroquine could augment the protective efficacy of the WKV of Plasmodium yoelii. The direct antimalarial effect of chloroquine on parasites during immunization could be excluded, as the administration of chloroquine or chloroquine plus alum every two weeks had a slight effect on parasitemia, and an immunization with NP-KLH (4-hydroxy-3-nitrophenylacetyl Keyhole Limpet Hemocyanin) plus chloroquine could significantly promote the generation of NP-specific antibodies. Additionally, alum was required for chloroquine to augment the immunogenicity of the pRBC lysate. Chloroquine did not promote the parasite-specific CD4+ T-cell responses, but significantly enhanced the WKV-induced germinal centre B cell reactions, class-switch recombination and secretion of functionally protective antibodies to plasmodium. The elevated parasite-specific antibodies were demonstrated to largely contribute to the chloroquine-enhanced protective immunity. Thus, we report that chloroquine could be used as an adjuvant to enhance the protective immunity of WKVs through promoting humoral responses.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Cloroquina/administração & dosagem , Vacinas Antimaláricas/imunologia , Plasmodium yoelii/imunologia , Vacinas de Produtos Inativados/imunologia , Compostos de Alúmen/administração & dosagem , Animais , Anticorpos Antiprotozoários/imunologia , Linfócitos B/imunologia , Feminino , Humanos , Switching de Imunoglobulina , Malária/imunologia , Vacinas Antimaláricas/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Plasmodium yoelii/crescimento & desenvolvimento , Vacinas de Produtos Inativados/administração & dosagem
18.
Carbohydr Polym ; 229: 115423, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31826462

RESUMO

Chitosan (CS) and its water-soluble derivatives, hydroxypropyltrimethyl ammonium chloride chitosan (HACC) and sulfated chitosan (SCS), were used as adjuvants of inactivated Newcastle disease (ND) vaccine. First, NDV-loaded and blank CS, HACC/CS and SCS nanoparticles were prepared. The particle sizes were respectively 343.43 ±â€¯4.12, 320.03 ±â€¯0.84, 156.2 ±â€¯9.29 nm and the zeta potentials were respectively +19.67 ±â€¯0.58, +18.3 ±â€¯0.5, -17.8 ±â€¯2.65 mV under the optimal conditions. Then chickens were immunized with nanoparticles or commercial inactivated oil emulsion vaccine. After immunization, the humoral immunity levels of the chickens were evaluated. The cellular immunity levels were determined by the quantification of cytokines, lymphocyte proliferation assay, the percentages of CD4+ and CD8+ T lymphocytes. Finally, the chickens were challenged with highly virulent virus. The results demonstrated that the humoral immunity levels in NDV-loaded CS and HACC/CS nanoparticles groups were lower than commercial vaccine but the cellular immunity levels are better. Moreover, the prevention effects of NDV-loaded CS and HACC/CS nanoparticles against highly virulent NDV are comparable to commercial vaccine. Our study provides the basis of developing HACC and CS as effective vaccine adjuvants.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Quitosana/análogos & derivados , Nanopartículas/administração & dosagem , Doença de Newcastle/prevenção & controle , Doenças das Aves Domésticas/prevenção & controle , Compostos de Amônio Quaternário/administração & dosagem , Vacinas de Produtos Inativados/administração & dosagem , Vacinas Virais/administração & dosagem , Animais , Galinhas , Quitosana/administração & dosagem , Citocinas/imunologia , Imunidade Humoral , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Camundongos , Vírus da Doença de Newcastle/imunologia , Células RAW 264.7 , Vacinação/métodos
19.
Virol J ; 16(1): 156, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842907

RESUMO

BACKGROUND: The foot-and-mouth disease (FMD) virus is classified into seven serotypes, of which the South African types have South African Territories (SAT)1, SAT2, and SAT3 that are prevalent in Africa. Especially SAT2 have spread to Arabian Peninsula and the Palestinian Autonomous Territories. Of these viruses, the incidence of SAT2 is the highest. It is important to prepare for the spread of the virus to other continents, even though most FMD viruses are bovine-derived. In particular, due to the high breeding density of pigs in Asia, more attention is usually paid to the immunity and protection of pigs than cattle. For this reason, this study investigated the immunity and protection of pigs against the SAT viruses. METHODS: Specific vaccines were developed for SAT1, SAT2, and SAT3 serotypes. These vaccine viruses were designed to be distinguished from the wild-type strain. An immunogenicity test was conducted using these vaccines in both cattle (n = 5/group) and pigs (n = 20/group). RESULTS: High virus-neutralizing titer of antibodies (> 1:100) was induced in only 2 weeks after the immunization of cattle with the individual vaccine for SAT1, SAT2 or SAT3, and a clear immune response was induced after the second immunization in pigs. When the vaccinated pigs (n = 4-5/group) were challenged by the homologous wild-type virus strain 4 weeks after immunization, all the pigs were protected from the challenge. CONCLUSIONS: This study confirmed that these vaccines can be used against SAT1, SAT2, and SAT3 viruses in cattle and pigs. The vaccine strains developed in this study are expected to be used as vaccines that can protect against FMD in the event of a future FMD outbreak in pigs in consideration of the situation in Asia.


Assuntos
Vírus da Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Doenças dos Suínos/prevenção & controle , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Bovinos , Doenças dos Bovinos/prevenção & controle , Vírus da Febre Aftosa/classificação , Sorogrupo , Suínos , Resultado do Tratamento , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vacinas Marcadoras/administração & dosagem , Vacinas Marcadoras/imunologia
20.
BMC Vet Res ; 15(1): 455, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852473

RESUMO

BACKGROUND: The threat of poultry-origin H6 avian influenza viruses to human health emphasizes the importance of monitoring their evolution. South Africa's H6N2 epidemic in chickens began in 2001 and two co-circulating antigenic sub-lineages of H6N2 could be distinguished from the outset. The true incidence and prevalence of H6N2 in the country has been difficult to determine, partly due to the continued use of an inactivated whole virus H6N2 vaccine and the inability to distinguish vaccinated from non-vaccinated birds on serology tests. In the present study, the complete genomes of 12 H6N2 viruses isolated from various farming systems between September 2015 and February 2019 in three major chicken-producing regions were analysed and a serological experiment was used to demonstrate the effects of antigenic mismatch in diagnostic tests. RESULTS: Genetic drift in H6N2 continued and antigenic diversity in sub-lineage I is increasing; no sub-lineage II viruses were detected. Reassortment patterns indicated epidemiological connections between provinces as well as different farming systems, but there was no reassortment with wild bird or ostrich influenza viruses. The sequence mismatch between the official antigens used for routine hemagglutination inhibition (HI) testing and circulating field strains has increased steadily, and we demonstrated that H6N2 field infections are likely to be missed. More concerning, sub-lineage I H6N2 viruses acquired three of the nine HA mutations associated with human receptor-binding preference (A13S, V187D and A193N) since 2002. Most sub-lineage I viruses isolated since 2015 acquired the K702R mutation in PB2 associated with the ability to infect humans, whereas prior to 2015 most viruses in sub-lineages I and II contained the avian lysine marker. All strains had an unusual HA0 motif of PQVETRGIF or PQVGTRGIF. CONCLUSIONS: The H6N2 viruses in South African chickens are mutating and reassorting amongst themselves but have remained a genetically pure lineage since they emerged more than 18 years ago. Greater efforts must be made by government and industry in the continuous isolation and characterization of field strains for use as HI antigens, new vaccine seed strains and to monitor the zoonotic threat of H6N2 viruses.


Assuntos
Galinhas/virologia , Vírus da Influenza A/genética , Influenza Aviária/virologia , Animais , Deriva Genética , Genoma Viral , Testes de Inibição da Hemaglutinação/veterinária , Vírus da Influenza A/classificação , Vírus Reordenados/genética , Testes Sorológicos , África do Sul/epidemiologia , Vacinas de Produtos Inativados
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