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1.
J Gen Virol ; 102(4)2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33913804

RESUMEN

The development of a vaccine to prevent Zika virus (ZIKV) infection has been one of the priorities in infectious disease research in recent years. There have been numerous attempts to develop an effective vaccine against ZIKV. It is imperative to choose the safest and the most effective ZIKV vaccine from all candidate vaccines to control this infection globally. We have employed a dual serotype of prime-boost recombinant vesicular stomatitis virus (VSV) vaccine strategy, to develop a ZIKV vaccine candidate, using a type 1 IFN-receptor knock-out (Ifnar-/-) mouse model for challenge studies. Prime vaccination with an attenuated recombinant VSV Indiana serotype (rVSVInd) carrying a genetically modified ZIKV envelope (E) protein gene followed by boost vaccination with attenuated recombinant VSV New Jersey serotype (rVSVNJ) carrying the same E gene induced robust adaptive immune responses. In particular, rVSV carrying the ZIKV E gene with the honeybee melittin signal peptide (msp) at the N terminus and VSV G protein transmembrane domain and cytoplasmic tail (Gtc) at the C terminus of the E gene induced strong protective immune responses. This vaccine regimen induced highly potent neutralizing antibodies and T cell responses in the absence of an adjuvant and protected Ifnar-/- mice from a lethal dose of the ZIKV challenge.


Asunto(s)
Virus de la Estomatitis Vesicular New Jersey/inmunología , Proteínas del Envoltorio Viral/inmunología , Vacunas Virales/inmunología , Infección por el Virus Zika/prevención & control , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Chlorocebus aethiops , Cricetinae , Células HEK293 , Humanos , Inmunidad , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Células Vero
2.
J Infect Dis ; 217(4): 637-640, 2018 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-29145619

RESUMEN

During influenza pandemics, secondary pneumococcal infections cause excessive mortality. However, the current 13-valent pneumococcal conjugate vaccine, PCV13, provides only limited protection against secondary infection. Therefore, a more effective pneumococcal vaccine is required to protect against secondary pneumococcal infections. Here, intranasal immunization with an attenuated pneumococcal pep27 mutant provides protection from influenza virus infection, and also from secondary pneumococcal challenge. These results indicate that mucosal immunity might be an effective way to reduce the morbidity and mortality due to secondary pneumococcal infections during influenza pandemics.


Asunto(s)
Infecciones por Orthomyxoviridae/prevención & control , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/inmunología , Administración Intranasal , Animales , Proteínas Bacterianas/genética , Peso Corporal , Modelos Animales de Enfermedad , Femenino , Ratones Endogámicos BALB C , Mutación , Infecciones por Orthomyxoviridae/complicaciones , Vacunas Neumococicas/genética , Análisis de Supervivencia , Resultado del Tratamiento , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/genética , Vacunas Atenuadas/inmunología , Factores de Virulencia/genética
3.
Immunol Cell Biol ; 90(4): 441-8, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-21709687

RESUMEN

Oxidative stress is implicated in the pathogenesis of allergic asthma and remains an attractive target for the prevention of the disease. Herein, we investigated the anti-inflammatory effects of apocynin, a NADPH oxidase (NOX) inhibitor, in both in vitro and in vivo allergen-induced experimental asthma mediated by Th2 hyperresponsiveness. Apocynin showed potential antioxidant activities and inhibitory effects on the activation of redox-sensitive transcription factors, such as NF-κB and AP-1, induced by pro-inflammatory stimuli, such as TNF-α, lipopolysaccharide and Poly I:C, and that inhibited the production of pro-inflammatory cytokines, such as TNF-α, IL-1ß and IL-6. In in vivo experimental asthma model, moreover, apocynin significantly attenuated ovalbumin-induced airway hyperresponsiveness and inflammation, as shown by the attenuation of total inflammatory cell and soluble product influx into bronchoalveolar lavage fluid, such as macrophages, eosinophils, IL-4, IL-5, IL-12, IL-13 and TNF-α. Apocynin also significantly reduced lung inflammation in the tissues. Altogether, these results suggest that apocynin may be useful in the treatment of inflammatory diseases induced by oxidative stress through NOX activity.


Asunto(s)
Acetofenonas/farmacología , NADPH Oxidasas/antagonistas & inhibidores , Neumonía/tratamiento farmacológico , Animales , Antiinflamatorios , Asma/tratamiento farmacológico , Asma/prevención & control , Citocinas , Humanos , Mediadores de Inflamación , Oxidación-Reducción , Estrés Oxidativo , Activación Transcripcional
4.
Vaccine ; 37(1): 90-98, 2019 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-30467061

RESUMEN

Streptococcus pneumoniae is a well-known pathogenic bacterium with a high mortality rate. Currently, a 23-valent pneumococcal polysaccharide vaccine (PPV23) and protein-conjugate vaccines (PCVs) are available on the market. However, both of these vaccines have limitations; specifically, PPV23 produces weak antibody responses in children younger than 2 years and PCVs only partially protect against secondary infection. Previously, we showed serotype-nonspecific protection by Δpep27 vaccine, but the reversion of Δpep27 to the wild type serotype during immunization cannot be excluded. To ensure the safety of the Δpep27 vaccine, comD, an important protein that activates competence, was inactivated, and the transformability of the double mutant (Δpep27ΔcomD) was determined. The transformation ability of this double mutant was successfully abolished. Δpep27ΔcomD immunization significantly increased the survival time after heterologous challenge(s), and diminished colonization levels independent of serotype, including a non-typeable strain (NCC1). Moreover, the double mutant was found to be highly safe in both normal and immunocompromised mice. In conclusion, this pneumococcal Δpep27ΔcomD vaccine appears to be a highly feasible and safe vaccine to prevent various types of pneumococcal infections.


Asunto(s)
Proteínas Bacterianas/inmunología , Mutación , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/genética , Administración Intranasal , Animales , Anticuerpos Antibacterianos/sangre , Proteínas Bacterianas/genética , Huésped Inmunocomprometido , Inmunoglobulina G/sangre , Masculino , Ratones , Ratones SCID , Infecciones Neumocócicas/inmunología , Vacunas Neumococicas/administración & dosificación , Serogrupo , Streptococcus pneumoniae/inmunología , Vacunas Atenuadas/administración & dosificación , Vacunas Atenuadas/inmunología
5.
Virulence ; 9(1): 1562-1575, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30246592

RESUMEN

Streptococcus pneumoniae (pneumococcus), the major pathogen for pneumonia, commonly colonizes the lung, but the mechanism underlying the coordination of virulence factors during invasion via the host protein remains poorly understood. Bacterial lysis releases the components of the cell wall, and triggers innate immunity and the subsequent secretion of pro-inflammatory cytokines. Previously, the virulence of the pep27 mutant was shown to be attenuated as a feasible candidate for vaccine development. However, the role of pep27 gene, belonging to the vancomycin-resistance locus (vncRS operon), in virulence, is largely unknown. This study demonstrates that transferrin in the host serum reduces the survival of the host during S. pneumoniae infections in mice. The exposure of the pneumococcal D39 strain to lactoferrin induced the vncRS operon, lysis, and subsequent in vivo cytokine production, resulting in lung inflammation. However, these responses were significantly attenuated in pneumococci harboring a mutation in pep27. Mechanistically, the VncS ligand, identified as lactoferrin, induced the vncRS operon and increased the in vivo mortality rates. Thus, serum-induced activation of vncRS plays an essential role in inducing pneumonia.


Asunto(s)
Proteínas Bacterianas/genética , Lactoferrina/genética , Operón , Neumonía Neumocócica/patología , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/patogenicidad , Células A549 , Animales , Citocinas , Humanos , Inmunidad Innata , Inflamación , Lactoferrina/farmacología , Pulmón/inmunología , Pulmón/microbiología , Masculino , Ratones Desnudos , Mutación , Streptococcus pneumoniae/efectos de los fármacos , Transferrina , Vancomicina/farmacología , Virulencia
6.
Arch Pharm Res ; 40(8): 885-893, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28735461

RESUMEN

Pneumonia is an inflammatory disease of the lung, responsible for high morbidity and mortality worldwide. It is caused by bacteria, viruses, fungi, or other microorganisms. Streptococcus pneumoniae, a gram-positive bacterium with over 90 serotypes, is the most common causative agent. Moreover, comorbid factors including heart failure, renal disease, and pulmonary disease could increase the risk of pneumococcal pneumonia. Since the advent of the pneumococcal vaccine in the 1980s, the incidence of pneumonia has decreased significantly. However, current vaccines confer only limited protection against serotypes included in the vaccine. Thus, to overcome this limitation, new types of pneumococcal vaccines have been sought and under clinical trials. In this review, we discuss pneumonia and summarize the various types of pneumococcal vaccines in progress.


Asunto(s)
Vacunas Neumococicas/administración & dosificación , Neumonía Neumocócica/prevención & control , Streptococcus pneumoniae/aislamiento & purificación , Animales , Humanos , Incidencia , Neumonía Neumocócica/epidemiología , Neumonía Neumocócica/microbiología , Factores de Riesgo
7.
Vaccine ; 34(51): 6481-6492, 2016 12 12.
Artículo en Inglés | MEDLINE | ID: mdl-27865564

RESUMEN

Streptococcus pneumoniae is comprised of more than 90 serotypes and is the major causative agent of pneumonia, which results in over 1million deaths worldwide every year. Currently available injectable vaccines can protect against only 13-23 serotypes, and result in decrease of colonization against vaccine serotypes. However, they are neither effective for inhibition of non-vaccine serotypes colonization nor inhibition against initial colonization in the nasopharynx against various serotypes. Thus, development of a vaccine conveying broader protection at the colonization stage is required. This study examined whether the Δpep27 mutant could provide protection at the nasopharynx against a broad range of serotypes. Δpep27 immunization stimulated secretion of IL-4, IL-10, TNF-α, INF-γ and IL-17, and significantly increased secretory-IgA levels in bronchoalveolar lavage fluid. Colonization and opsonophagocytosis assays demonstrated that Δpep27 immunization could protect against many heterologous infections, including non-typeable strains, at the nasopharynx, and prompted efficient killing of heterologous strains, suggesting that Δpep27 immunization provides a wide range of cross-protection. Furthermore, Δpep27 immunization significantly increased both the survival rate and the level of IgG 3months post-immunization, demonstrating long-lasting immunity. Thus, Δpep27 could serve as a highly feasible mucosal vaccine once it is further developed into a non-transformable strain.


Asunto(s)
Portador Sano/prevención & control , Citocinas/metabolismo , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/inmunología , Streptococcus pneumoniae/inmunología , Animales , Anticuerpos Antibacterianos/análisis , Anticuerpos Antibacterianos/sangre , Proteínas Bacterianas/genética , Líquido del Lavado Bronquioalveolar/inmunología , Modelos Animales de Enfermedad , Eliminación de Gen , Inmunoglobulina A Secretora/análisis , Inmunoglobulina G/sangre , Masculino , Ratones , Ratones Endogámicos BALB C , Nasofaringe/microbiología , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/genética , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/aislamiento & purificación , Análisis de Supervivencia , Factores de Tiempo
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