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1.
F1000Res ; 92020.
Artículo en Inglés | MEDLINE | ID: mdl-32399192

RESUMEN

Seasonal influenza remains a major public health problem, responsible for hundreds of thousands of deaths every year, mostly of elderly people. Despite the wide availability of vaccines, there are multiple problems decreasing the effectiveness of vaccination programs. These include viral variability and hence the requirement to match strains by estimating which will become prevalent each season, problems associated with vaccine and adjuvant production, and the route of administration as well as the perceived lower vaccine efficiency in older adults. Clinical protection is still suboptimal for all of these reasons, and vaccine uptake remains too low in most countries. Efforts to improve the effectiveness of influenza vaccines include developing universal vaccines independent of the circulating strains in any particular season and stimulating cellular as well as humoral responses, especially in the elderly. This commentary assesses progress over the last 3 years towards achieving these aims. Since the beginning of 2020, an unprecedented international academic and industrial effort to develop effective vaccines against the new coronavirus SARS-CoV-2 has diverted attention away from influenza, but many of the lessons learned for the one will synergize with the other to mutual advantage. And, unlike the SARS-1 epidemic and, we hope, the SARS-CoV-2 pandemic, influenza will not be eliminated and thus efforts to improve influenza vaccines will remain of crucial importance.


Asunto(s)
Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Betacoronavirus , Infecciones por Coronavirus , Humanos , Pandemias , Neumonía Viral
2.
Viruses ; 12(5)2020 05 08.
Artículo en Inglés | MEDLINE | ID: mdl-32397182

RESUMEN

In the midst of the ongoing COVID-19 coronavirus pandemic, influenza virus remains a major threat to public health due to its potential to cause epidemics and pandemics with significant human mortality. Cases of H7N9 human infections emerged in eastern China in 2013 and immediately raised pandemic concerns as historically, pandemics were caused by the introduction of new subtypes into immunologically naïve human populations. Highly pathogenic H7N9 cases with severe disease were reported recently, indicating the continuing public health threat and the need for a prophylactic vaccine. Here we review the development of recombinant influenza virus-like particles (VLPs) as vaccines against H7N9 virus. Several approaches to vaccine development are reviewed including the expression of VLPs in mammalian, plant and insect cell expression systems. Although considerable progress has been achieved, including demonstration of safety and immunogenicity of H7N9 VLPs in the human clinical trials, the remaining challenges need to be addressed. These challenges include improvements to the manufacturing processes, as well as enhancements to immunogenicity in order to elicit protective immunity to multiple variants and subtypes of influenza virus.


Asunto(s)
Subtipo H7N9 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Vacunas de Partículas Similares a Virus/genética , Animales , Antígenos Virales/inmunología , Ensayos Clínicos como Asunto , Epítopos , Antígenos de Histocompatibilidad Clase II , Humanos
3.
Cell Host Microbe ; 27(5): 695-698, 2020 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-32407707

RESUMEN

As scientists consider SARS-CoV-2 vaccine design, we discuss problems that may be encountered and how to tackle them by what we term "rational vaccine design." We further discuss approaches to pan-coronavirus vaccines. We draw on experiences from recent research on several viruses including HIV and influenza, as well as coronaviruses.


Asunto(s)
Anticuerpos Antivirales/inmunología , Antígenos Virales/inmunología , Betacoronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/prevención & control , Vacunas Virales/inmunología , Vacunas contra el SIDA/inmunología , Vacunas contra el SIDA/normas , Infecciones por Coronavirus/inmunología , Humanos , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/normas , Neumonía Viral/inmunología , Proyectos de Investigación/tendencias
4.
Int J Nanomedicine ; 15: 2071-2083, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32273703

RESUMEN

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.


Asunto(s)
Adyuvantes Inmunológicos/química , Sistemas de Liberación de Medicamentos/métodos , Emulsiones/química , Vacunas contra la Influenza/administración & dosificación , Nanoestructuras/química , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Animales , Emulsiones/administración & dosificación , Emulsiones/farmacología , Femenino , Subtipo H3N2 del Virus de la Influenza A , Vacunas contra la Influenza/inmunología , Ratones Endogámicos ICR , Aceites/química , Infecciones por Orthomyxoviridae/prevención & control , Tamaño de la Partícula , Aceite de Soja/química , Vacunas de Productos Inactivados , Agua/química
5.
J Med Life ; 13(1): 37-44, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32341699

RESUMEN

This study empirically illustrates the mechanism by which epidemiological effect measures and statistical evidence can be misleading in the presence of Simpson's paradox and identify possible alternative methods of analysis to manage the paradox. Three scenarios of observational study designs, including cross-sectional, cohort, and case-control approaches, are simulated. In each scenario, data are generated, and various methods of epidemiological and statistical analyses are undertaken to obtain empirical results that illustrate Simpson's paradox and mislead conclusions. Rational methods of analysis are also performed to illustrate how to avoid pitfalls and obtain valid results. In the presence of Simpson's paradox, results from analyses in overall data contradict the findings from all subgroups of the same data. This paradox occurs when distributions of confounding characteristics are unequal in the groups being compared. Data analysis methods which do not take confounding factor into account, including epidemiological 2×2 table analysis, independent samples t-test, Wilcoxon rank-sum test, chi-square test, and univariable regression analysis, cannot manage the problem of Simpson's paradox and mislead research conclusions. Mantel-Haenszel procedure and multivariable regression methods are examples of rational analysis methods leading to valid results. Therefore, Simpson's paradox arises as a consequence of extreme unequal distributions of a specific inherent characteristic in groups being compared. Analytical methods which take control of confounding effect must be applied to manage the paradox and obtain valid research evidence regarding the causal association.


Asunto(s)
Estudios Epidemiológicos , Estudios Observacionales como Asunto , Proyectos de Investigación , Estadística como Asunto , Estudios de Casos y Controles , Café , Estudios de Cohortes , Estudios Transversales , Odontólogos , Femenino , Humanos , Vacunas contra la Influenza/inmunología , Masculino , Análisis Multivariante , Análisis de Regresión
8.
PLoS One ; 15(3): e0227962, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32155152

RESUMEN

OBJECTIVE: Since the 2009 influenza pandemic, Latin American (LA) countries have strengthened their influenza surveillance systems. We analyzed influenza genetic sequence data from the 2017 through 2018 Southern Hemisphere (SH) influenza season from selected LA countries, to map the availability of influenza genetic sequence data from, and to describe, the 2017 through 2018 SH influenza seasons in LA. METHODS: We analyzed influenza A/H1pdm09, A/H3, B/Victoria and B/Yamagata hemagglutinin sequences from clinical samples from 12 National Influenza Centers (NICs) in ten countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Ecuador, Mexico, Paraguay, Peru and Uruguay) with a collection date from epidemiologic week (EW) 18, 2017 through EW 43, 2018. These sequences were generated by the NIC or the WHO Collaborating Center (CC) at the U.S Centers for Disease Control and Prevention, uploaded to the Global Initiative on Sharing All Influenza Data (GISAID) platform, and used for phylogenetic reconstruction. FINDINGS: Influenza hemagglutinin sequences from the participating countries (A/H1pdm09 n = 326, A/H3 n = 636, B n = 433) were highly concordant with the genetic groups of the influenza vaccine-recommended viruses for influenza A/H1pdm09 and influenza B. For influenza A/H3, the concordance was variable. CONCLUSIONS: Considering the constant evolution of influenza viruses, high-quality surveillance data-specifically genetic sequence data, are important to allow public health decision makers to make informed decisions about prevention and control strategies, such as influenza vaccine composition. Countries that conduct influenza genetic sequencing for surveillance in LA should continue to work with the WHO CCs to produce high-quality genetic sequence data and upload those sequences to open-access databases.


Asunto(s)
Evolución Molecular , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Orthomyxoviridae/genética , Pandemias/prevención & control , Conjuntos de Datos como Asunto , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Humanos , Vacunas contra la Influenza/inmunología , Gripe Humana/epidemiología , Gripe Humana/microbiología , América Latina/epidemiología , Orthomyxoviridae/inmunología , Orthomyxoviridae/aislamiento & purificación , Filogenia
9.
Artículo en Inglés | MEDLINE | ID: mdl-32178606

RESUMEN

As part of its role in the World Health Organization's (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne received a total of 3993 human influenza-positive samples during 2018. Viruses were analysed for their antigenic, genetic and antiviral susceptibility properties. Selected viruses were propagated in qualified cells or hens' eggs for use as potential seasonal influenza vaccine virus candidates. In 2018, influenza A(H1)pdm09 viruses predominated over influenza A(H3) and B viruses, accounting for a total of 53% of all viruses analysed. The majority of A(H1)pdm09, A(H3) and influenza B viruses analysed at the Centre were found to be antigenically similar to the respective WHO-recommended vaccine strains for the Southern Hemisphere in 2018. However, phylogenetic analysis indicated that a significant proportion of circulating A(H3) viruses had undergone genetic drift relative to the WHO-recommended vaccine strain for 2018. Of 2864 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, three A(H1)pdm09 viruses showed highly reduced inhibition by oseltamivir, while one B/Victoria virus showed highly reduced inhibition by both oseltamivir and zanamivir.


Asunto(s)
Antivirales/farmacología , Virus de la Influenza A , Virus de la Influenza B , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Animales , Antígenos Virales , Australia/epidemiología , Pollos , Farmacorresistencia Viral , Humanos , Virus de la Influenza A/efectos de los fármacos , Virus de la Influenza A/genética , Virus de la Influenza B/efectos de los fármacos , Virus de la Influenza B/genética , Vacunas contra la Influenza/uso terapéutico , Oseltamivir , Filogenia , Organización Mundial de la Salud , Zanamivir
10.
Science ; 367(6480)2020 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-32079747

RESUMEN

Current influenza vaccines only confer protection against homologous viruses. We synthesized pulmonary surfactant (PS)-biomimetic liposomes encapsulating 2',3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), an agonist of the interferon gene inducer STING (stimulator of interferon genes). The adjuvant (PS-GAMP) vigorously augmented influenza vaccine-induced humoral and CD8+ T cell immune responses in mice by simulating the early phase of viral infection without concomitant excess inflammation. Two days after intranasal immunization with PS-GAMP-adjuvanted H1N1 vaccine, strong cross-protection was elicited against distant H1N1 and heterosubtypic H3N2, H5N1, and H7N9 viruses for at least 6 months while maintaining lung-resident memory CD8+ T cells. Adjuvanticity was then validated in ferrets. When alveolar epithelial cells (AECs) lacked Sting or gap junctions were blocked, PS-GAMP-mediated adjuvanticity was substantially abrogated in vivo. Thus, AECs play a pivotal role in configuring heterosubtypic immunity.


Asunto(s)
Materiales Biomiméticos , Vacunas contra la Influenza/inmunología , Nanopartículas , Nucleótidos Cíclicos/administración & dosificación , Infecciones por Orthomyxoviridae/prevención & control , Surfactantes Pulmonares/inmunología , Vacunación/métodos , Adyuvantes Inmunológicos/administración & dosificación , Administración Intranasal , Animales , Materiales Biomiméticos/administración & dosificación , Linfocitos T CD8-positivos/inmunología , Hurones , Memoria Inmunológica , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H3N2 del Virus de la Influenza A/inmunología , Subtipo H5N1 del Virus de la Influenza A/inmunología , Subtipo H7N9 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/administración & dosificación , Liposomas , Proteínas de la Membrana/agonistas , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Mutantes , Nanopartículas/administración & dosificación , Nucleótidos Cíclicos/farmacología , Surfactantes Pulmonares/administración & dosificación
11.
Nat Commun ; 11(1): 791, 2020 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-32034141

RESUMEN

The conserved hemagglutinin (HA) stem has been a focus of universal influenza vaccine efforts. Influenza A group 1 HA stem-nanoparticles have been demonstrated to confer heterosubtypic protection in animals; however, the protection does not extend to group 2 viruses, due in part to differences in glycosylation between group 1 and 2 stems. Here, we show that introducing the group 2 glycan at Asn38HA1 to a group 1 stem-nanoparticle (gN38 variant) based on A/New Caledonia/20/99 (H1N1) broadens antibody responses to cross-react with group 2 HAs. Immunoglobulins elicited by the gN38 variant provide complete protection against group 2 H7N9 virus infection, while the variant loses protection against a group 1 H5N1 virus. The N38HA1 glycan thus is pivotal in directing antibody responses by controlling access to group-determining stem epitopes. Precise targeting of stem-directed antibody responses to the site of vulnerability by glycan repositioning may be a step towards achieving cross-group influenza protection.


Asunto(s)
Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Vacunas contra la Influenza/inmunología , Nanopartículas/química , Polisacáridos/química , Animales , Anticuerpos Antivirales/inmunología , Especificidad de Anticuerpos , Asparagina/química , Asparagina/metabolismo , Anticuerpos ampliamente neutralizantes/inmunología , Reacciones Cruzadas , Epítopos/inmunología , Femenino , Glicosilación , Glicoproteínas Hemaglutininas del Virus de la Influenza/metabolismo , Inmunoglobulinas/inmunología , Subtipo H7N9 del Virus de la Influenza A/patogenicidad , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/prevención & control
12.
PLoS One ; 15(2): e0227719, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32012159

RESUMEN

BACKGROUND: On-line hemodiafiltration (HDF) clears more azotemic toxins compared to high-flux hemodialysis (HD). The response to vaccination is impaired in dialysis patients. We wished to determine whether the immune responses to influenza vaccine in dialysis patients treated by HDF were stronger than those treated by HD. MATERIALS AND METHODS: We conducted a prospective cohort study in chronic dialysis patients during the 2016 and 2017 influenza seasons. All participants received a single standard dose of trivalent influenza vaccine, and we studied the elicited humoral immune response by hemagglutination inhibition test, and cell-mediated immune response by enumeration of lymphocyte cellular markers and proliferation assays. RESULTS: We immunized 60 end-stage renal disease (ESRD) patients: 42 (70%) treated with HD and 18 patients (30%) with HDF. The median (interquartile range) age was 65.0 (55.0-74.5) years. All patients developed seroprotection to at least one influenza vaccine strain at one month post-vaccination, and did not differ between groups. By logistic regression, age was the only factor independently associated with seroconversion to all vaccine strains (odds ratio 0.89, 95% confidence interval 0.80-0.98; p = 0.022). Seroprotection to all vaccine strains was sustained for longer in patients treated with HDF, and the results remained the same after age adjustment. For cellular immune response, patients who seroconverted to all vaccine strains had higher CD38+ T cell subpopulations pre-vaccination. Patients treated by HDF had higher lymphocyte proliferation to circulating influenza A strains. CONCLUSIONS: Seroconversion to all influenza vaccine strains was associated with age. Patients treated with HDF demonstrated seroprotection was sustained for longer compared to those treated by HD and greater lymphocyte proliferation to circulating influenza A strains. These encouraging results for HDF require confirmation in a larger dialysis population. TRIAL REGISTRATION: ClinicalTrial.gov, NCT04122222.


Asunto(s)
Inmunidad Innata , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Fallo Renal Crónico/prevención & control , Adulto , Anciano , Azotemia/inmunología , Azotemia/patología , Proliferación Celular/genética , Femenino , Pruebas de Inhibición de Hemaglutinación , Hemodiafiltración , Humanos , Vacunas contra la Influenza/inmunología , Gripe Humana/inmunología , Gripe Humana/virología , Fallo Renal Crónico/inmunología , Fallo Renal Crónico/virología , Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Diálisis Renal , Linfocitos T/inmunología , Vacunación , Vacunas/administración & dosificación
13.
MMWR Morb Mortal Wkly Rep ; 69(7): 177-182, 2020 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-32078591

RESUMEN

During the 2019-20 influenza season, influenza-like illness (ILI)* activity first exceeded the national baseline during the week ending November 9, 2019, signaling the earliest start to the influenza season since the 2009 influenza A(H1N1) pandemic. Activity remains elevated as of mid-February 2020. In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (1). During each influenza season, CDC estimates seasonal influenza vaccine effectiveness in preventing laboratory-confirmed influenza associated with medically attended acute respiratory illness (ARI). This interim report used data from 4,112 children and adults enrolled in the U.S. Influenza Vaccine Effectiveness Network (U.S. Flu VE Network) during October 23, 2019-January 25, 2020. Overall, vaccine effectiveness (VE) against any influenza virus associated with medically attended ARI was 45% (95% confidence interval [CI] = 36%-53%). VE was estimated to be 50% (95% CI = 39%-59%) against influenza B/Victoria viruses and 37% (95% CI = 19%-52%) against influenza A(H1N1)pdm09, indicating that vaccine has significantly reduced medical visits associated with influenza so far this season. Notably, vaccination provided substantial protection (VE = 55%; 95% CI = 42%-65%) among children and adolescents aged 6 months-17 years. Interim VE estimates are consistent with those from previous seasons, ranging from 40%-60% when influenza vaccines were antigenically matched to circulating viruses. CDC recommends that health care providers continue to administer influenza vaccine to persons aged ≥6 months because influenza activity is ongoing, and the vaccine can still prevent illness, hospitalization, and death associated with currently circulating influenza viruses as well as other influenza viruses that might circulate later in the season.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Subtipo H3N2 del Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/aislamiento & purificación , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Vigilancia de la Población , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Lactante , Vacunas contra la Influenza/inmunología , Gripe Humana/epidemiología , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Estaciones del Año , Estados Unidos/epidemiología , Adulto Joven
14.
Medicine (Baltimore) ; 99(7): e19095, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32049815

RESUMEN

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.


Asunto(s)
Inmunogenicidad Vacunal/efectos de los fármacos , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Escualeno/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/inmunología , Gripe Humana/virología , Masculino , Persona de Mediana Edad , Polisorbatos/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Seroconversión/efectos de los fármacos , Escualeno/administración & dosificación , Vacunas de Productos Inactivados , Adulto Joven
15.
PLoS One ; 15(2): e0228029, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32045419

RESUMEN

Influenza A (H1N1) pdm09 virus emerged in North America in 2009 and has been established as a seasonal strain in humans. After an antigenic stasis of about six years, new antigenically distinct variants of the virus emerged globally in 2016 necessitating a change in the vaccine formulation for the first time in 2017. Herein, we analyzed thirty-eight HA sequences of influenza A (H1N1) pdm09 strains isolated in Kenya during 2015-2018 seasons, to evaluate their antigenic and molecular properties based on the HA1 sub-unit. Our analyses revealed that the A (H1N1) pdm09 strains that circulated in Kenya during this period belonged to genetic clade 6B, subclade 6B.1 and 6B.2. The Kenyan 2015 and 2016 isolates differed from the vaccine strain A/California/07/2009 at nine and fourteen antigenic sites in the HA1 respectively. Further, those isolated in 2017 and 2018 correspondingly varied from A/Michigan/45/2015 vaccine strain at three and fifteen antigenic sites. The predicted vaccine efficacy of A/California/07/2009 against Kenyan 2015/2016 was estimated to be 32.4% while A/Michigan/45/2015 showed estimated vaccine efficacies of 39.6% - 41.8% and 32.4% - 42.1% against Kenyan 2017 and 2018 strains, respectively. Hemagglutination-inhibition (HAI) assay using ferret post-infection reference antiserum showed that the titers for the Kenyan 2015/2016 isolates were 2-8-fold lower compared to the vaccine strain. Overall, our results suggest the A (H1N1) pdm09 viruses that circulated in Kenya during 2015/2016 influenza seasons were antigenic variants of the recommended vaccine strains, denoting sub-optimal vaccine efficacy. Additionally, data generated point to a swiftly evolving influenza A (H1N1) pdm09 virus in recent post pandemic era, underscoring the need for sustained surveillance coupled with molecular and antigenic analyses, to inform appropriate and timely influenza vaccine update.


Asunto(s)
Antígenos Virales/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Subtipo H1N1 del Virus de la Influenza A/clasificación , Subtipo H1N1 del Virus de la Influenza A/inmunología , Filogenia , Subunidades de Proteína/inmunología , Secuencia de Aminoácidos , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Vacunas contra la Influenza/inmunología , Kenia , Homología de Secuencia de Aminoácido , Organización Mundial de la Salud
16.
Arch Virol ; 165(4): 891-911, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32060794

RESUMEN

Pandemics caused by influenza A virus (IAV) are responsible for the deaths of millions of humans around the world. One of these pandemics occurred in Mexico in 2009. Despite the impact of IAV on human health, there is no effective vaccine. Gene mutations and translocation of genome segments of different IAV subtypes infecting a single host cell make the development of a universal vaccine difficult. The design of immunogenic peptides using bioinformatics tools could be an interesting strategy to increase the success of vaccines. In this work, we used the predicted amino acid sequences of the neuraminidase (NA) and hemagglutinin (HA) proteins of different IAV subtypes to perform multiple alignments, epitope predictions, molecular dynamics simulations, and experimental validation. Peptide selection was based on the following criteria: promiscuity, protein surface exposure, and the degree of conservation among different medically relevant IAV strains. These peptides were tested using immunological assays to test their ability to induce production of antibodies against IAV. We immunized rabbits and mice and measured the levels of IgG and IgA antibodies in serum samples and nasal washes. Rabbit antibodies against the peptides P11 and P14 (both of which are hybrids of NA and HA) recognized HA from both group 1 (H1, H2, and H5) and group 2 (H3 and H7) IAV and also recognized the purified NA protein from the viral stock (influenza A Puerto Rico/916/34). IgG antibodies from rabbits immunized with P11 and P14 were capable of recognizing viral particles and inhibited virus hemagglutination. Additionally, intranasal immunization of mice with P11 and P14 induced specific IgG and IgA antibodies in serum and nasal mucosa, respectively. Interestingly, the IgG antibodies were found to have neutralizing capability. In conclusion, the peptides designed through in silico studies were validated in experimental assays.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Secuencia de Aminoácidos , Animales , Biología Computacional , Epítopos/química , Epítopos/genética , Epítopos/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Humanos , Inmunización , Virus de la Influenza A/química , Virus de la Influenza A/genética , Vacunas contra la Influenza/química , Vacunas contra la Influenza/genética , Gripe Humana/inmunología , Gripe Humana/virología , Ratones , Ratones Endogámicos BALB C , Neuraminidasa/química , Neuraminidasa/genética , Neuraminidasa/inmunología , Conejos , Alineación de Secuencia , Proteínas Virales/química , Proteínas Virales/genética , Proteínas Virales/inmunología
17.
PLoS Comput Biol ; 16(2): e1007683, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32069282

RESUMEN

Influenza A/H3N2 is a rapidly evolving virus which experiences major antigenic transitions every two to eight years. Anticipating the timing and outcome of transitions is critical to developing effective seasonal influenza vaccines. Using a published phylodynamic model of influenza transmission, we identified indicators of future evolutionary success for an emerging antigenic cluster and quantified fundamental trade-offs in our ability to make such predictions. The eventual fate of a new cluster depends on its initial epidemiological growth rate--which is a function of mutational load and population susceptibility to the cluster--along with the variance in growth rate across co-circulating viruses. Logistic regression can predict whether a cluster at 5% relative frequency will eventually succeed with ~80% sensitivity, providing up to eight months advance warning. As a cluster expands, the predictions improve while the lead-time for vaccine development and other interventions decreases. However, attempts to make comparable predictions from 12 years of empirical influenza surveillance data, which are far sparser and more coarse-grained, achieve only 56% sensitivity. By expanding influenza surveillance to obtain more granular estimates of the frequencies of and population-wide susceptibility to emerging viruses, we can better anticipate major antigenic transitions. This provides added incentives for accelerating the vaccine production cycle to reduce the lead time required for strain selection.


Asunto(s)
Antígenos Virales/química , Biología Computacional , Subtipo H3N2 del Virus de la Influenza A/química , Subtipo H3N2 del Virus de la Influenza A/inmunología , Gripe Humana/virología , Antígenos Virales/inmunología , Área Bajo la Curva , Evolución Biológica , Análisis por Conglomerados , Simulación por Computador , Epítopos , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Humanos , Vacunas contra la Influenza/inmunología , Gripe Humana/inmunología , Filogenia , Análisis de Secuencia de ADN , Procesos Estocásticos
18.
Nat Commun ; 11(1): 315, 2020 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-31949137

RESUMEN

Standard inactivated influenza vaccines are poorly immunogenic in immunologically naive healthy young children, who are particularly vulnerable to complications from influenza. For them, there is an unmet need for better influenza vaccines. Oil-in-water emulsion-adjuvanted influenza vaccines are promising candidates, but clinical trials yielded inconsistent results. Here, we meta-analyze randomized controlled trials with efficacy data (3 trials, n = 15,310) and immunogenicity data (17 trials, n = 9062). Compared with non-adjuvanted counterparts, adjuvanted influenza vaccines provide a significantly better protection (weighted estimate for risk ratio of RT-PCR-confirmed influenza: 0.26) and are significantly more immunogenic (weighted estimates for seroprotection rate ratio: 4.6 to 7.9) in healthy immunologically naive young children. Nevertheless, in immunologically non-naive children, adjuvanted and non-adjuvanted vaccines provide similar protection and are similarly immunogenic. These results indicate that oil-in-water emulsion adjuvant improves the efficacy of inactivated influenza vaccines in healthy young children at the first-time seasonal influenza vaccination.


Asunto(s)
Adyuvantes Inmunológicos/química , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Aceites/química , Agua/química , Anticuerpos Antivirales/sangre , Formación de Anticuerpos , Niño , Bases de Datos Factuales , Emulsiones , Humanos , Inmunidad , Vacunas contra la Influenza/sangre , Vacunas contra la Influenza/química , Gripe Humana/inmunología , Orthomyxoviridae , Vacunación
19.
Proc Natl Acad Sci U S A ; 117(2): 1119-1128, 2020 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-31888983

RESUMEN

Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated "hot" tumors demonstrate higher treatment response rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies. Innovative approaches that make tumors hot can have immediate impact particularly if they repurpose drugs with additional cancer-unrelated benefits. The seasonal influenza vaccine is recommended for all persons over 6 mo without prohibitive contraindications, including most cancer patients. Here, we report that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts "cold" tumors to hot, generates systemic CD8+ T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade. Importantly, intratumoral vaccination also provides protection against subsequent active influenza virus lung infection. Surprisingly, a squalene-based adjuvanted vaccine maintains intratumoral regulatory B cells and fails to improve antitumor responses, even while protecting against active influenza virus lung infection. Adjuvant removal, B cell depletion, or IL-10 blockade recovers its antitumor effectiveness. Our findings propose that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy.


Asunto(s)
Inmunoterapia/métodos , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/uso terapéutico , Inyecciones Intralesiones , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Linfocitos B , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Linfocitos T CD8-positivos/inmunología , Humanos , Inmunidad Celular , Subtipo H1N1 del Virus de la Influenza A/inmunología , Gripe Humana , Interleucina-10 , Pulmón/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Ratones , Ratones Endogámicos C57BL , Proteínas Represoras/genética , Estaciones del Año , Piel , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Escualeno/administración & dosificación , Microambiente Tumoral/efectos de los fármacos , Vacunación
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