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1.
Medicina (Kaunas) ; 57(3)2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33803295

RESUMO

The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic warrants an imperative necessity for effective and safe vaccination, to restrain Coronavirus disease 2019 (COVID-19) including transmissibility, morbidity, and mortality. In this regard, intensive medical and biological research leading to the development of an arsenal of vaccines, albeit incomplete preconditioned evaluation, due to emergency. The subsequent scientific gap raises some concerns in the medical community and the general public. More specifically, the accelerated vaccine development downgraded the value of necessary pre-clinical studies to elicit medium- and long-term beneficial or harmful consequences. Previous experience and pathophysiological background of coronaviruses' infections and vaccine technologies, combined with the global vaccines' application, underlined the obligation of a cautious and qualitative approach, to illuminate potential vaccination-related adverse events. Moreover, the high SARS-CoV-2 mutation potential and the already aggregated genetical alterations provoke a rational vagueness and uncertainty concerning vaccines' efficacy against dominant strains and the respective clinical immunity. This review critically summarizes existing evidence and queries regarding SARS-CoV-2 vaccines, to motivate scientists' and clinicians' interest for an optimal, individualized, and holistic management of this unprecedented pandemic.


Assuntos
/uso terapêutico , /prevenção & controle , Adjuvantes Imunológicos/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Aprovação de Drogas , Avaliação Pré-Clínica de Medicamentos , Juramento Hipocrático , Humanos , Efeitos Adversos de Longa Duração/induzido quimicamente , Modelos Animais , Medição de Risco , Vacinas de Produtos Inativados/uso terapêutico , Vacinas Sintéticas/uso terapêutico
2.
Muscle Nerve ; 63(3): 294-303, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33471383

RESUMO

The clinical course of neuromuscular disorders (NMDs) can be affected by infections, both in immunocompetent individuals, and in those with reduced immunocompetence due to immunosuppressive/immunomodulating therapies. Infections and immunizations may also trigger NMDs. There is a potential for reduced efficacy of immunizations in patients with reduced immunocompetence. The recent vaccination program for coronavirus disease-2019 (COVID-19) raises several questions regarding the safety and efficacy of this vaccine in individuals with NMDs. In this Practice Topic article, we address the role of vaccine-preventable infections in NMDs and the safety and efficacy of immunization in individuals with NMDs, with emphasis on vaccination against COVID-19.


Assuntos
/uso terapêutico , Imunossupressores/efeitos adversos , Doenças Neuromusculares/terapia , Doenças Preveníveis por Vacina/prevenção & controle , /complicações , /imunologia , Síndrome de Guillain-Barré/epidemiologia , Síndrome de Guillain-Barré/etiologia , Humanos , Imunocompetência/imunologia , Hospedeiro Imunocomprometido/imunologia , Fatores Imunológicos/efeitos adversos , Doenças Neuromusculares/epidemiologia , Doenças Neuromusculares/imunologia , Vacinas Atenuadas/uso terapêutico , Vacinas de Produtos Inativados/uso terapêutico
3.
Cell ; 182(3): 713-721.e9, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32778225

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens global public health. The development of a vaccine is urgently needed for the prevention and control of COVID-19. Here, we report the pilot-scale production of an inactivated SARS-CoV-2 vaccine candidate (BBIBP-CorV) that induces high levels of neutralizing antibodies titers in mice, rats, guinea pigs, rabbits, and nonhuman primates (cynomolgus monkeys and rhesus macaques) to provide protection against SARS-CoV-2. Two-dose immunizations using 2 µg/dose of BBIBP-CorV provided highly efficient protection against SARS-CoV-2 intratracheal challenge in rhesus macaques, without detectable antibody-dependent enhancement of infection. In addition, BBIBP-CorV exhibits efficient productivity and good genetic stability for vaccine manufacture. These results support the further evaluation of BBIBP-CorV in a clinical trial.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Avaliação Pré-Clínica de Medicamentos/métodos , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Vacinas de Produtos Inativados/uso terapêutico , Vacinas Virais/uso terapêutico , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Betacoronavirus/genética , Chlorocebus aethiops , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Feminino , Cobaias , Imunogenicidade da Vacina , Macaca fascicularis , Macaca mulatta , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Filogenia , Pneumonia Viral/virologia , Coelhos , Ratos , Ratos Wistar , Vacinas de Produtos Inativados/efeitos adversos , Células Vero , Vacinas Virais/efeitos adversos
4.
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
5.
Vaccine ; 37(36): 5171-5176, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31377075

RESUMO

Influenza is a major medically attended respiratory illness. The impact of influenza on morbidity and mortality is particularly high in the elderly. Immunosenescence attenuates the immune response of influenza vaccine in the elderly. High-dose influenza vaccine contains 60 µg of hemagglutinin per strain, four times more compared with standard-dose (SD) influenza vaccine. This study is a phase I clinical trial investigating the immunogenicity and safety of the GC3114, high-dose, quadrivalent inactivated influenza vaccine (HD-QIV) in healthy adults aged 19-64 years during the 2017-2018 season. Seroprotection rates of HD-QIV were 100.0% for A/H1N1, 96.67% for A/H3N2, 83.33% for B/Yamagata, and 96.67% for B/Victoria. Seroconversion rate for A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains were 86.67%, 90.0%, 53.33%, and 53.33%, respectively, in the HD-QIV group. The post-/pre-vaccination geometric mean titer ratio (GMTR) was 15.28 for A/H1N1, 8.19 for A/H3N2, 3.56 for B/Yamagata, and 3.03 for B/Victoria in the HD-QIV group. Seroconversion rate and post-/pre-vaccination GMTR for A/H3N2 were significantly higher in the HD-QIV group than in the SD-QIV group (control). No serious adverse events were reported. In conclusion, GC3114 was safe, well-tolerated, and immunogenic in healthy adults. Clinical Trials Identifier: NCT03357263.


Assuntos
Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/uso terapêutico , Adulto , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H1N1/patogenicidade , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/patogenicidade , Vírus da Influenza B/imunologia , Vírus da Influenza B/patogenicidade , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Vacinas de Produtos Inativados/imunologia
6.
Vaccine ; 37(36): 5211-5217, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31375437

RESUMO

Observational cohort studies in high-income settings have suggested that vaccination order may affect children's subsequent risk of a heterologous infection, with live vaccines reducing and inactivated vaccines (given on their own or with a live vaccine), increasing the risk. We used the self-controlled case-series method, which automatically controls for the individual level confounding to which such cohort studies are prone, to test this hypothesis. We compared the relative incidence (RI) of infections post-vaccination in two calendar periods in England; in Period 1 (September 2002-August 2006) live measles, mumps, rubella (MMR) vaccine was given on its own and in Period 2 (September 2006-April 2010) inactivated vaccines (7-valent pneumococcal conjugate vaccine (PCV7) and sometimes the combined Haemophilus influenzae type b/meningococcal group C vaccine (Hib-MenC)) were given concomitantly with MMR. Admissions for an infection of the upper or lower respiratory tract, gastrointestinal system or other site in children aged 11-23 months were selected from the Hospital Episode Statistics database in England and linked to child health immunisation histories. The analysis included a total of 24,144 infections in 21,067 children in Period 1 and 36,880 in 31,616 children in Period 2. The RI of admission for any infection in Period 1 was 1.00 (95% confidence interval 0.95-1.06) compared with 0.95 (95% confidence interval 0.90-1.00) in Period 2. Comparing the two periods showed no evidence of a difference in the relative incidence estimates with a ratio of RI of 0.94 (95% confidence interval 0.87-1.02), RIs within 90 days of vaccination were 0.94 (0.91-0.97) in Period 1 and 0.94 (0.91-0.97) in Period 2, consistent with a temporary healthy vaccinee effect. In conclusion, we found no evidence to support the hypothesis that there is a reduction in heterologous infections after MMR on its own or an increase after MMR given concomitantly with an inactivated vaccine.


Assuntos
Vacina contra Sarampo-Caxumba-Rubéola/uso terapêutico , Vacinas de Produtos Inativados/uso terapêutico , Inglaterra , Feminino , Humanos , Esquemas de Imunização , Lactente , Masculino , Sarampo/imunologia , Sarampo/prevenção & controle , Vacina contra Sarampo-Caxumba-Rubéola/imunologia , Caxumba/imunologia , Caxumba/prevenção & controle , Rubéola (Sarampo Alemão)/imunologia , Rubéola (Sarampo Alemão)/prevenção & controle , Vacinas Conjugadas/imunologia , Vacinas Conjugadas/uso terapêutico , Vacinas de Produtos Inativados/imunologia
7.
Vaccine ; 37(36): 5161-5170, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31375440

RESUMO

OBJECTIVE: In response to the emergence of influenza viruses with pandemic potential, we evaluated a swine-origin influenza A/H3N2 variant (H3N2v) vaccine in children. STUDY DESIGN: This multicenter phase II open-label study assessed the safety and immunogenicity of two doses, 21 days apart, of investigational unadjuvanted subvirion monovalent inactivated H3N2v vaccine administered via intramuscular injection. Children 6-35 months of age received 7.5mcg or 15mcg of hemagglutinin (HA)/dose; children 3-17 years of age received 15mcg HA/dose. Safety and reactogenicity were assessed by measuring the occurrence of solicited injection site and systemic reactions in the 7 days after each vaccination; adverse events were assessed for 42 days and serious adverse events for 7 months after the first vaccination. Immunogenicity was evaluated by measuring hemagglutination inhibition (HAI) and neutralizing (Neut) antibodies to H3N2v prior to and 21 days after each vaccination. Cross-reactivity against seasonal H3N2 strains was evaluated. RESULTS: The H3N2v vaccine was well tolerated. Transient mild to moderate injection site tenderness, pain and erythema was observed, with the most commonly reported systemic reactogenicity being irritability in children 6-35 months, and headache and fatigue in children 9-17 years old. Children 6-35 months old, whether they received 7.5mcg or 15mcg/dose, had low HAI and Neut antibody responses after two doses compared to older children. Children under 9 years of age required two doses of vaccine to demonstrate a response, while 9-17 year olds responded well after one dose. Previous influenza vaccination and older age were associated with higher immune responses to H3N2v vaccine. Children 9-17 years of age also developed cross-reactive antibodies against recent seasonal H3N2 influenza viruses. CONCLUSION: The H3N2v vaccine was safe and immunogenic in children and adolescents. Age-related increases in immunogenicity against H3N2v and seasonal H3N2 viruses were observed, suggesting prior priming via infection and/or immunization. Clinical trial registry: The trial is registered with clinicaltrial.gov: NCT02100436.


Assuntos
Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/patogenicidade , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/uso terapêutico , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico , Adolescente , Adulto , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/metabolismo , Criança , Pré-Escolar , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Vacinas contra Influenza/efeitos adversos , Masculino , Vacinas de Produtos Inativados/efeitos adversos , Adulto Jovem
8.
Comp Immunol Microbiol Infect Dis ; 66: 101329, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31437687

RESUMO

The Eurasian wild boar (Sus scrofa) is a reservoir for tuberculosis (TB) in which vaccination is a valuable tool for control. We evaluated the protection and immune response achieved by homologous and heterologous regimes administering BCG and heat-inactivated Mycobacterium bovis (IV). Twenty-one wild boar piglets were randomly allocated in five groups: Control, homologous BCG, homologous IV, heterologous IV-BCG, heterologous BCG-IV. Significant 67% and 66% total lesion score reductions were detected in homologous IV (IVx2) and heterologous IV-BCG groups when compared with Control group (F4,16 = 6.393, p = 0.003; Bonferroni Control vs IVx2 p = 0.026, Tukey Control vs IV-BCG p = 0.021). No significant differences were found for homologous BCG (although a 48% reduction in total lesion score was recorded) and BCG-IV (3% reduction). Heterologous regimes did not improve protection over homologous regimes in the wild boar model and showed variable results from no protection to similar protection as homologous regimes. Therefore, homologous regimes remain the best option to vaccinate wild boar against TB. Moreover, vaccine sequence dramatically influenced the outcome underlining the relevance of studying the effects of prior sensitization in the outcome of vaccination.


Assuntos
Vacina BCG/uso terapêutico , Esquemas de Imunização , Sus scrofa/imunologia , Tuberculose/veterinária , Vacinação/veterinária , Animais , Anticorpos Antibacterianos/sangue , Vacina BCG/administração & dosagem , Citocinas/imunologia , Masculino , Viabilidade Microbiana/imunologia , Mycobacterium bovis , Distribuição Aleatória , Suínos , Tuberculose/prevenção & controle , Vacinas de Produtos Inativados/uso terapêutico
9.
Vaccine ; 37(36): 5203-5210, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31351795

RESUMO

Infectious bursal disease (IBD) is an acute, highly contagious immunosuppressive disease that affects young birds causing important economic losses in the poultry industry worldwide. Strict hygiene management together with effective vaccination programs are the most important strategies to prevent Infectious bursal disease virus entry in poultry production facilities. Hyperimmunisation of dams with inactivated vaccines just before the laying period provides passive immunity to the progeny that protects them during the critical first few weeks after hatching before vaccination with live attenuated virus takes place. In the present study, a safe and economic plant-based vaccine candidate against IBD intended for breeder hens was evaluated. We demonstrated that the recombinant immunogen is effective as booster for previously primed hens since it increases specific antibodies against VP2 that are transmitted to the offspring with titres and decay rate similar to those achieved by inactivated vaccine. Moreover, these maternally derived antibodies have virus neutralising activity and are able to confer protection against challenge in progeny, as evidenced by absence of bursal damage and low viral titres in this organ. Taking into account the disadvantages of inactivated vaccines as well as the benefits of plants as expression systems, such as time and cost efficiency, lower risk of contamination from animal pathogens and nearly unlimited scalability, a plant-based subunit IBD vaccine represents a viable alternative in the veterinary field.


Assuntos
Infecções por Birnaviridae/prevenção & controle , Plantas/metabolismo , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/prevenção & controle , Vacinas Atenuadas/uso terapêutico , Vacinas de Produtos Inativados/uso terapêutico , Vacinas Virais/uso terapêutico , Animais , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/metabolismo , Infecções por Birnaviridae/imunologia , Galinhas , Vírus da Doença Infecciosa da Bursa/imunologia , Vírus da Doença Infecciosa da Bursa/patogenicidade , Vacinas de Produtos Inativados/imunologia
10.
Vaccine ; 37(36): 5341-5349, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31351798

RESUMO

A suitable animal model of CVA16 infection is crucial in order to understand its pathogenesis and to help develop antiviral vaccines or screen therapeutic drugs. The neonatal mouse model has a short sensitivity period to CA16 infection, which is a major limitation. In this study, we demonstrate that adult (60-day-old) gerbils are susceptible to CVA16 infection at high doses (108.0 TCID50). A clinical isolate strain of CVA16 was inoculated intraperitoneally into adult gerbils, which subsequently developed significant clinical symptoms, including hind limb weakness, paralysis of one or both hind limbs, tremors, and eventual death from neurological disorders. Real-time RT-PCR revealed that viral loads in the spinal cord and brainstem were higher than those in other organs/tissues. Histopathological changes, such as neuronal degeneration, neuronal loss, and neuronophagia, were observed in the spinal cord, brainstem, and heart muscle, along with necrotizing myositis. Gerbils receiving both prime and boost immunizations of alum adjuvant inactivated vaccine exhibited no clinical signs of disease or mortality following challenge by CVA16, whereas 80% of control animals showed obvious clinical signs, including slowness, paralysis of one or both hind limbs, and eventual death, suggesting that the CVA16 vaccine can fully protect gerbils against CVA16 challenge. These results demonstrate that an adult gerbil model provides us with a useful tool for studying the pathogenesis and evaluating antiviral reagents of CVA16 infection. The development of this animal model would also be conducive to screening promising CVA16 vaccine candidates as well as further vaccination evaluation.


Assuntos
Enterovirus/imunologia , Enterovirus/patogenicidade , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico , Vacinas Virais/imunologia , Vacinas Virais/uso terapêutico , Animais , Animais Recém-Nascidos , Anticorpos Neutralizantes/imunologia , Modelos Animais de Doenças , Feminino , Gerbillinae , Masculino , Carga Viral/imunologia
11.
Vaccine ; 37(36): 5382-5389, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31345642

RESUMO

This study examined the protective efficacy of and immune response to a nasal influenza vaccine combined with a novel mucosal oligodeoxynucleotide (ODN) adjuvant, CpG ODN G9.1 (G9.1), in a model of infection limited to the upper respiratory tract (URT) and a model of infection in the lower respiratory tract (LRT). Mice were nasally primed with an A/California/7/2009 (Cal7) split vaccine (X179A) plus G9.1 and were then nasally given a booster with X179A alone. When mice were challenged with either a large (infection of the LRT) or small (infection limited to the URT) volume of live Cal7 influenza virus, mice nasally given G9.1 combined with X179A had a markedly higher rate of protection against infection limited to the URT. Moreover, this group of mice promptly recovered from an infection of the LRT. When mice were subcutaneously (s.c.) given X179A as a current form of vaccination, they had no protection from an infection limited to the URT but they did recover from an infection of the LRT. The patterns of protection were closely correlated with influenza virus-specific mucosal secretory IgA (SIgA) or serum IgG antibody (Ab) responses. Thus, SIgA Abs responses play an important role in protection from an infection limited to the URT while influenza virus-specific serum IgG Ab responses help to protect from an infection of the LRT. A finding of note is that lungs from mice nasally given G9.1 had low levels of type I IFN-associated protein- and transcription factor-specific mRNA expression. These results suggest that nasal G9.1 can be used as an effective and safe mucosal adjuvant for influenza vaccines since this nasal vaccine system elicits both mucosal SIgA and serum IgG Ab responses that provide complete protection without inducing potent inflammatory responses.


Assuntos
Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Oligodesoxirribonucleotídeos/imunologia , Adjuvantes Imunológicos , Administração Intranasal , Animais , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/metabolismo , Feminino , Humanos , Imunoglobulina A/imunologia , Imunoglobulina A/metabolismo , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/uso terapêutico , Cinética , Camundongos , Camundongos Endogâmicos BALB C , Orthomyxoviridae/imunologia , Orthomyxoviridae/patogenicidade , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico
12.
Vet Immunol Immunopathol ; 213: 109887, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307668

RESUMO

Chlamydia abortus produces ovine enzootic abortion (OEA). Symptoms are not observed until the organism colonises the placenta, eventually causing abortion. Infected animals become carriers and will shed the organism in the following oestruses. This process suggests that sex hormones might play an important role in the physiopathology of OEA, affecting the success of chlamydial clearance and also jeopardising the effectiveness of vaccination. However, the mechanisms through which sex hormones are involved in chlamydial pathogenicity remain unclear. The aim of this study, therefore, was to determine the effect of progesterone on the immune response against C. abortus and on the protection conferred by an experimental inactivated vaccine in sheep. Eighteen sheep were ovariectomised and divided into four groups: vaccinated and progesterone-treated (V-PG), vaccinated and non-treated (V-NT), non-vaccinated and non-treated (NV-NT) and non-vaccinated and progesterone-treated sheep (NV-PG). Animals from both PG groups were treated with commercial medroxyprogesterone acetate impregnated intravaginal sponges before and during the vaccination (V-PG) or just before challenge (NV-PG). The animals from both V groups were subcutaneously immunised with an experimental inactivated vaccine, which was seen to confer high protection in previous studies. All sheep were challenged intratracheally with C. abortus strain AB7 and were sacrificed on day 8 post-infection. Morbidity was measured as the variation in rectal temperature and samples of sera were collected for antibody and cytokine (IFN-γ and IL-10) analysis by commercial ELISA. In addition, lung and lymph node samples were collected for chlamydial detection by qPCR and for histopathological and immunohistochemical analyses. Sheep from the V-PG group showed less severe or no lesions and lower morbidity than the other groups. They also had the highest abundance of regulatory T-cells. The sheep from V-NT also manifested high antibody levels against C. abortus and less severe lesions than those observed in non-vaccinated sheep, which showed high morbidity, low antibody levels and severe lesions, especially in NV-NT. These results confirm the effectiveness of the experimental vaccine employed and suggest that progesterone could enhance the effect.


Assuntos
Vacinas Bacterianas/uso terapêutico , Infecções por Chlamydia/veterinária , Imunidade Humoral , Progesterona/administração & dosagem , Doenças dos Ovinos/imunologia , Aborto Animal/imunologia , Aborto Animal/prevenção & controle , Animais , Anticorpos Antibacterianos/sangue , Vacinas Bacterianas/imunologia , Chlamydia/imunologia , Infecções por Chlamydia/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Ovinos , Doenças dos Ovinos/microbiologia , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico
13.
Vaccine ; 37(30): 4047-4054, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31186191

RESUMO

OBJECTIVES: We assessed the vaccine effectiveness (VE) of inactivated influenza vaccine (IIV) by vaccine dose in children aged 6 months to 12 years for whom two doses are recommended in Japan to ascertain the appropriate vaccine doses. METHODS: VE was assessed according to a test-negative case-control design based on rapid influenza diagnostic test (RIDT) results. Children aged 6 months to 12 years with a fever ≥38 °C who had received an RIDT in outpatient clinics of 24 hospitals were enrolled for all five seasons since 2013/14. VE by vaccine dose (none vs. once or twice, and once vs. twice) was analyzed. RESULTS: In the dose analysis, 20,033 children were enrolled. Both one- and two-dose regimens significantly reduced cases in preventing any influenza, influenza A, and influenza B, but there was no significant difference in adjusted VE between one- and two-dose regimens overall (adjusted OR, 0.560 [95% CI, 0.505-0.621], 0.550 [95% CI, 0.516-0.586]), 0.549 [95% CI, 0.517-0.583], and 1.014 [95% CI, 0.907-1.135], for none vs. once, none vs. twice, none vs. once or twice, and once vs. twice for any influenza, respectively). Both one- and two-dose regimens significantly reduced cases with any influenza and influenza A every season. Also, both regimens significantly reduced cases of any influenza, influenza A, and influenza B among children aged 1-12 years, especially among those aged 1-5 years. In the 2013/14, 2015/16, and 2016/17 seasons, however, only the two-dose regimen was significantly effective in preventing influenza B. Both one- and two-dose regimens significantly reduced cases involving hospitalization due to any influenza and influenza A. CONCLUSIONS: Both one- and two-doses regimens of IIV were effective in preventing influenza for children aged 6 months to 12 years. The two-dose regimen was more effective against influenza B in some seasons.


Assuntos
Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Vacinas de Produtos Inativados/uso terapêutico , Criança , Pré-Escolar , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Influenza Humana/virologia , Masculino , Vacinação
14.
Vaccine ; 37(30): 4055-4060, 2019 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-31196683

RESUMO

OBJECTIVE: Evaluate whether a guideline recommending Live Attenuated Influenza Vaccine (LAIV) for children 2 years and older with asthma increased risks for lower respiratory events (LREs), within 21 or 42 days of vaccination, as compared to standard guidelines to administer Inactivated Influenza Vaccine (IIV) in children with asthma. METHODS: This was a pre/post guideline retrospective cohort study of children ages 2-17 years with asthma and receiving one or more influenza vaccines in two large medical groups from 2007 to 2016. Both groups recommended IIV in the pre-period; in 2010, one group implemented a guideline recommending LAIV for all children, including those with asthma. Main outcomes were medically attended LREs within 21 and 42 days after influenza immunization. Analysis used a generalized estimating equation regression to estimate the ratio of rate ratios (RORs) comparing pre/post events between LAIV guideline and control group. RESULTS: The cohort included 7851 influenza vaccinations in 4771 children with asthma. Among patients in the LAIV guideline group, the proportion receiving LAIV increased from 23% to 68% post-guideline implementation, versus an increase from 7 to 11% in the control group. Age and baseline asthma severity adjusted ROR showed no increase in LREs, primarily asthma exacerbations, following implementation of the LAIV guideline: overall aROR (95% Confidence Interval): 0.74 (0.43-1.29) for LRE within 21 days of vaccination, 0.77 (0.53-1.14) for LRE within 42 days of vaccination. For the subset of children ages 2-4 years aROR: 0.92 (0.34-2.53) for LRE within 21 days of vaccination and 0.94 (0.49-1.82) for LRE within 42 days of vaccination; for children 5-18 years aROR (95% CI): 0.58 (0.26-1.30) for LRE within 21 days of vaccination and 0.67 (0.37-1.23) for LRE within 42 days. CONCLUSION: In a large cohort of children with asthma, a guideline recommending LAIV rather than IIV did not increase LREs following vaccination.


Assuntos
Asma/imunologia , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Vacinas Atenuadas/efeitos adversos , Vacinas Atenuadas/uso terapêutico , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/uso terapêutico , Adolescente , Criança , Pré-Escolar , Feminino , Guias como Assunto , Humanos , Masculino , Estudos Retrospectivos
15.
BMC Infect Dis ; 19(1): 453, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31117986

RESUMO

BACKGROUND: High hemagglutination inhibition (HAI) and neuraminidase inhibition (NAI) titers are generally associated with reduced influenza risk. While repeated influenza vaccination reduces seroresponse, vaccine effectiveness is not always reduced. METHODS: During the 2007-2008 influenza season, a randomized, placebo-controlled trial (FLUVACS) evaluated the efficacies of live-attenuated (LAIV) and inactivated influenza vaccines (IIV) among healthy adults aged 18-49 in Michigan; IIV vaccine efficacy (VE) and LAIV VE against influenza disease were estimated at 68% and 36%. Using the principal stratification/VE moderation framework, we analyzed data from this trial to assess how each VE varied by HAI or NAI responses to vaccination observed for vaccinated individuals and predicted counterfactually for placebo recipients. We also assessed how each VE varied with pre-vaccination/baseline variables including HAI titer, NAI titer, and vaccination history. RESULTS: IIV VE appeared to increase with Day 30 post-vaccination HAI titer, albeit not significantly (p=0.20 and estimated VE 14.4%, 70.5%, and 85.5% at titer below the assay lower quantification limit, 512, and 4096 (maximum)). Moreover, IIV VE increased significantly with Day 30 post-vaccination NAI titer (p=0.040), with estimated VE zero at titer 10 and 92.2% at highest titer 640. There was no evidence that fold-change in post-vaccination HAI or NAI titer associated with IIV VE (p=0.76, 0.38). For LAIV, there was no evidence that VE associated with post-vaccination or fold-rise HAI or NAI titers (p-values >0.40). For IIV, VE increased with increasing baseline NAI titer in those previously vaccinated, but VE decreased with increasing baseline NAI titer in those previously unvaccinated. In contrast, for LAIV, VE did not depend on previous vaccination or baseline HAI or NAI titer. CONCLUSIONS: Future efficacy trials should measure baseline and post-vaccination antibody titers in both vaccine and control/placebo recipients, enabling analyses to better elucidate correlates of vaccine- and natural-protection. TRIAL REGISTRATION: ClinicalTrials.gov NCT00538512. October 1, 2007.


Assuntos
Testes de Inibição da Hemaglutinação , Vacinas contra Influenza/uso terapêutico , Vacinas Atenuadas/uso terapêutico , Vacinas de Produtos Inativados/uso terapêutico , Adolescente , Adulto , Humanos , Imunogenicidade da Vacina , Testes Imunológicos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Pessoa de Meia-Idade , Neuraminidase/antagonistas & inibidores , Placebos , Fatores de Tempo , Vacinas Atenuadas/imunologia , Vacinas de Produtos Inativados/imunologia
16.
J Fish Dis ; 42(7): 1057-1064, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31087342

RESUMO

Lumpfish (Cyclopterus lumpus), a native fish of the North Atlantic Ocean, is utilized as cleaner fish to biocontrol sea lice infestations in Atlantic salmon aquaculture. However, bacterial infections are affecting cleaner fish performance. Vibrio anguillarum, the aetiological agent of vibriosis, is one of the most frequent bacterial infections in lumpfish, and effective vaccine programmes against this pathogen have been identified as a high priority for lumpfish. Vibrogen-2 is a commercial polyvalent bath vaccine that contains formalin-inactivated cultures of V. anguillarum serotypes O1 and O2, and Vibrio ordalii. In this study, we evaluated Vibrogen-2 efficacy in lumpfish against a local isolated V. anguillarum strain. Two groups of 125 lumpfish were bath-immunized, bath-boost-immunized at four weeks post-primary immunization, and intraperitoneally (i.p.) boost-immunized at eight weeks post-primary immunization. The control groups were i.p. mock-immunized with PBS. Twenty-seven weeks post-primary immunization, the fish were i.p. challenged with 10 or 100 times the V. anguillarum J360 LD50 dose. After the challenge, survival was monitored daily, and samples of tissues were collected at ten days post-challenge. Commercial vaccine Vibrogen-2 reduced V. anguillarum tissue colonization and delayed mortality but did not confer immune protection to C. lumpus against the V. anguillarum i.p. challenge.


Assuntos
Vacinas Bacterianas/uso terapêutico , Doenças dos Peixes/prevenção & controle , Peixes/microbiologia , Vibrioses/veterinária , Vibrio/imunologia , Animais , Aquicultura , Vacinas Bacterianas/imunologia , Agentes de Controle Biológico , Doenças dos Peixes/imunologia , Imersão , Dose Letal Mediana , Vacinação/métodos , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico , Vibrioses/imunologia , Vibrioses/prevenção & controle
17.
Arch Virol ; 164(6): 1501-1513, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30888563

RESUMO

Foot-and-mouth disease (FMD) is a major worldwide viral disease in animals, affecting the national and international trade of livestock and animal products and leading to high economic losses and social consequences. Effective control measures of FMD involve prevention through vaccination with inactivated vaccines. These inactivated vaccines, unfortunately, require short-term protection and cold-chain and high-containment facilities. Major advances and pursuit of hot topics in vaccinology and vectorology are ongoing, involving peptide vaccines, DNA vaccines, live vector vaccines, and novel attenuated vaccines. DIVA capability and marker vaccines are very important in differentiating infected animals from vaccinated animals. This review focuses on updating the research progress of these novel vaccines, summarizing their merits and including ideas for improvement.


Assuntos
Vírus da Febre Aftosa/imunologia , Febre Aftosa/prevenção & controle , Gado/virologia , Vacinas Virais/uso terapêutico , Animais , Bovinos , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/virologia , Febre Aftosa/imunologia , Vírus da Febre Aftosa/genética , Doenças dos Cavalos/prevenção & controle , Doenças dos Cavalos/virologia , Cavalos , Ovinos , Doenças dos Ovinos/prevenção & controle , Doenças dos Ovinos/virologia , Vacinas de DNA/imunologia , Vacinas de DNA/uso terapêutico , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico , Vacinas de Subunidades/imunologia , Vacinas de Subunidades/uso terapêutico , Vacinas de Partículas Semelhantes a Vírus/uso terapêutico , Vacinas Virais/imunologia
18.
Hum Vaccin Immunother ; 15(5): 1183-1190, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30779680

RESUMO

INTRODUCTION: Enterovirus A71(EV-A71)-associated hand, foot, and mouth disease (HFMD) has been reported worldwide, and poses a particularly heavy burden on patients, families, and society in China. Three Chinese companies have licensed inactivated EV-A71 vaccines, all of which have demonstrated good efficacy for preventing EV-A71-associated disease in clinical trials. However, real-world performance of EV-A71 vaccine has not been evaluated. METHODS: We used a test-negative design case-control study to estimate vaccine effectiveness (VE) against medically attended EV-A71-associated HFMD. Subjects were children 5 years of age and under who had been in health facilities participating in the HFMD case and virologic surveillance platforms in Beijing. Enterovirus infections were laboratory confirmed, and EV-A71 vaccination status was extracted from electronic immunization records. Children testing positive for EV-A71 were cases; controls were children testing negative for EV-A71 infection. Logistic regression was used to estimate VE. We assessed sensitivity of VE estimates to control group inclusion criteria by repeating the regression analyses with two alternative control groups. RESULTS: A total of 2,184 HFMD patients aged 5 years and under were enrolled in the study; 24 were severe, and 2,160 were mild. For severe cases, two-dose VE estimate was 100% (95% CI: -68.1%, 100%). For mild cases, 1-dose and 2-dose adjusted VE estimates were 69.8% and 83.7%, respectively. Two-dose VE estimates varied by less than 4 percentage points regardless of control group definition. CONCLUSIONS: Our findings suggested the vaccines performed well in the real world for children 5 years of age and under in Beijing, China.


Assuntos
Enterovirus Humano A , Doença de Mão, Pé e Boca/terapia , Potência de Vacina , Vacinas Virais/uso terapêutico , Pequim , Estudos de Casos e Controles , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Vacinação , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/uso terapêutico , Vacinas Virais/administração & dosagem
19.
Biochem Biophys Res Commun ; 511(2): 253-259, 2019 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-30777330

RESUMO

Inactivated vaccines are widely used for prevention of viral disease. Both humoral and cellular immune responses have been shown to play important roles in the control and clearance of virus infections. CpG motif containing oligodeoxynucleotides (ODN) have recently gained considerable interest and been used as vaccine adjuvant due to their potent abilities to modulate host immune response. In this study, CpG-ODN adjuvant and inactivated viral particles of enterovirus 71 (EV71) were co-encapsulated into nanoparticles (NP) generated by using protamine sulfate (PS) and carboxymethyl ß-glucan (CMG) through a self-assembly approach. The administration of EV71 nanovaccine elicited not only specific anti-EV71 neutralizing antibody response, but also cellular immune response characterized by strong productions of IFN-α and IFN-γ. The results suggest that CMG/PS-based nanovehicles hold a great potential to be a novel platform for nanovaccine development against viral disease.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Enterovirus Humano A/imunologia , Infecções por Enterovirus/prevenção & controle , Oligodesoxirribonucleotídeos/administração & dosagem , Vacinas de Produtos Inativados/administração & dosagem , Vacinas Virais/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Animais , Infecções por Enterovirus/imunologia , Infecções por Enterovirus/virologia , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Nanopartículas/química , Oligodesoxirribonucleotídeos/uso terapêutico , Protaminas/química , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico , Vacinas Virais/imunologia , Vacinas Virais/uso terapêutico , beta-Glucanas/química
20.
Pediatrics ; 143(2)2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30617239

RESUMO

BACKGROUND: Researchers in observational studies of vaccine effectiveness (VE) in which they compared quadrivalent live attenuated vaccine (LAIV4) and inactivated influenza vaccine (IIV) among children and adolescents have shown inconsistent results, and the studies have been limited by small samples. METHODS: We combined data from 5 US studies from 2013-2014 through 2015-2016 to compare the VE of LAIV4 and IIV against medically attended, laboratory-confirmed influenza among patients aged 2 to 17 years by influenza season, subtype, age group, and prior vaccination status. The VE of IIV or LAIV4 was calculated as 100% × (1 - odds ratio), comparing the odds of vaccination among patients who were influenza-positive to patients who were influenza-negative from adjusted logistic regression models. Relative effectiveness was defined as the odds of influenza comparingLAIV4 and IIV recipients. RESULTS: Of 17 173 patients aged 2 to 17 years, 4579 received IIV, 1979 received LAIV4, and 10 615 were unvaccinated. Against influenza A/H1N1pdm09, VE was 67% (95% confidence interval [CI]: 62% to 72%) for IIV and 20% (95% CI: -6% to 39%) for LAIV4. Results were similar when stratified by vaccination in the previous season. LAIV4 recipients had significantly higher odds of influenza A/H1N1pdm09 compared with IIV recipients (odds ratio 2.66; 95% CI: 2.06 to 3.44). LAIV4 and IIV had similar effectiveness against influenza A/H3N2 and B. Our overall findings were consistent when stratified by influenza season and age group. CONCLUSIONS: From this pooled individual patient-level data analysis, we found reduced effectiveness of LAIV4 against influenza A/H1N1pdm09 compared with IIV, which is consistent with published results from the individual studies included.


Assuntos
Vacinas contra Influenza/uso terapêutico , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Influenza Humana/diagnóstico , Masculino , Resultado do Tratamento , Estados Unidos/epidemiologia , Vacinas Atenuadas/uso terapêutico , Vacinas de Produtos Inativados/uso terapêutico
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