RESUMEN
Current influenza vaccine strategies have yet to overcome significant obstacles, including rapid antigenic drift of seasonal influenza viruses, in generating efficacious long-term humoral immunity. Due to the necessity of germinal center formation in generating long-lived high affinity antibodies, the germinal center has increasingly become a target for the development of novel or improvement of less-efficacious vaccines. However, there remains a major gap in current influenza research to effectively target T follicular helper cells during vaccination to alter the germinal center reaction. In this study, we used a heterologous infection or immunization priming strategy to seed an antigen-specific memory CD4+ T cell pool prior to influenza infection in mice to evaluate the effect of recalled memory T follicular helper cells in increased help to influenza-specific primary B cells and enhanced generation of neutralizing antibodies. We found that heterologous priming with intranasal infection with acute lymphocytic choriomeningitis virus (LCMV) or intramuscular immunization with adjuvanted recombinant LCMV glycoprotein induced increased antigen-specific effector CD4+ T and B cellular responses following infection with a recombinant influenza strain that expresses LCMV glycoprotein. Heterologously primed mice had increased expansion of secondary Th1 and Tfh cell subsets, including increased CD4+ TRM cells in the lung. However, the early enhancement of the germinal center cellular response following influenza infection did not impact influenza-specific antibody generation or B cell repertoires compared to primary influenza infection. Overall, our study suggests that while heterologous infection or immunization priming of CD4+ T cells is able to enhance the early germinal center reaction, further studies to understand how to target the germinal center and CD4+ T cells specifically to increase long-lived antiviral humoral immunity are needed.
Asunto(s)
Linfocitos T CD4-Positivos , Centro Germinal , Vacunas contra la Influenza , Infecciones por Orthomyxoviridae , Animales , Centro Germinal/inmunología , Ratones , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Linfocitos T CD4-Positivos/inmunología , Anticuerpos Antivirales/inmunología , Ratones Endogámicos C57BL , Linfocitos B/inmunología , Memoria Inmunológica , Células T de Memoria/inmunología , Inmunización/métodos , Femenino , Antígenos Virales/inmunologíaRESUMEN
Background: Vitamin E from palm oil, known as the tocotrienol-rich fraction (TRF), has been shown to have immune-enhancing activity. To date, only one dose of TRF (400 mg daily) has been tested in a clinical trial. The proposed study will evaluate the immune-enhancing activity effects of lower doses (200, 100 and 50 mg) in a clinical trial using an influenza vaccine as the immunological challenge. Methods: A single-centre, randomised, parallel, double-blinded, placebo-controlled clinical trial with balance allocation involving five arms will be conducted. The healthy volunteers recruited will be randomly assigned to one of the arms, and they will be asked to take the respective supplements (400 mg, 200 mg, 100 mg, 50 mg of TRF or placebo) daily with their dinner. The volunteers will receive the influenza vaccine after four weeks. They will be asked to return to the study site four weeks later. A blood sample will be taken for the study at baseline, four and eight weeks. Primary outcome measures will be antibody levels to influenza, blood leucocyte profile and cytokine production. Secondary outcomes will be correlating plasma vitamin E levels with immune responses, plasma proteins and gene expression patterns. The findings from this study will be published in relevant peer-reviewed journals and presented at relevant national and international scientific meetings. Conclusions: The recent world events have created the awareness of having a healthy and functional immune system. Nutrition plays an important role in helping the immune system to function optimally. This study will show the effects of lower doses of TRF in boosting the immune response of healthy individuals and also elucidate the mechanisms through which TRF exerts its immune-enhancing effects. Clinical trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) [ ACTRN12622000844741] dated 15 June 2022. Protocol version: 2.
Asunto(s)
Suplementos Dietéticos , Voluntarios Sanos , Vacunas contra la Influenza , Aceite de Palma , Tocotrienoles , Humanos , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Tocotrienoles/administración & dosificación , Aceite de Palma/administración & dosificación , Gripe Humana/prevención & control , Gripe Humana/inmunología , Método Doble Ciego , Vacunación , Adulto , Masculino , Vitamina E , Femenino , Agentes Inmunomoduladores , Citocinas/sangreRESUMEN
Elevated body mass index (BMI) has been linked to severe influenza illness and impaired vaccine immunogenicity, but the relationship between BMI and clinical vaccine effectiveness (VE) is less well described. This secondary analysis of data from a test-negative study of outpatients with acute respiratory illness assessed BMI and VE against medically attended, PCR-confirmed influenza over seven seasons (2011-12 through 2017-18). Vaccination status was determined from electronic medical records (EMR) and self-report; BMI was estimated from EMR-documented height and weight categorized for adults as obesity (≥ 30 kg/m2), overweight (25-29 kg/m2), or normal and for children based on standardized z-scales. Current season VE by virus type/subtype was estimated separately for adults and children. Pooled VE for all seasons was calculated as 1-adjusted odds ratios from logistic regression with an interaction term for BMI and vaccination. Among 28,089 adults and 12,380 children, BMI category was not significantly associated with VE against outpatient influenza for any type/subtype. Adjusted VE against A/H3N2, A/H1N1pdm09, and B in adults ranged from 16-31, 46-54, and 44-57%, and in children from 29-34, 57-65, and 50-55%, respectively, across the BMI categories. Elevated BMI was not associated with reduced VE against laboratory confirmed, outpatient influenza illness.
Asunto(s)
Índice de Masa Corporal , Vacunas contra la Influenza , Gripe Humana , Humanos , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Masculino , Femenino , Gripe Humana/prevención & control , Gripe Humana/inmunología , Gripe Humana/epidemiología , Adulto , Niño , Persona de Mediana Edad , Adolescente , Eficacia de las Vacunas , Anciano , Vacunación , Adulto Joven , Preescolar , Obesidad , Subtipo H3N2 del Virus de la Influenza A/inmunologíaRESUMEN
BACKGROUND The purpose of the study was to determine the level of antihemagglutinin antibodies in the serum of patients in the geriatric population in Doctor's Surgery NZOZ Nucleus Warsaw, Poland, during the epidemic season 2021/2022 using the hemagglutination inhibition assay (HAI), according to anti-influenza and anti-COVID-19 vaccination, age, and sex. MATERIAL AND METHODS Serum samples taken from 256 patients aged 65 to 99 years were examined for anti-hemagglutinin antibodies and protective levels of antibodies against antigens: A/Victoria/2570/2019 (H1N1)pdm09, A/Cambodia/e0826360/2020(H3N2), B/Washington/02/2019 (B/Victoria lineage), and B/Phuket/3073/2013 (B/Yamagata lineage) of the quadrivalent influenza vaccine for epidemic season 2021/2022. RESULTS The highest protective level, ie, the percentage of people with antibody titers ≥40 was 87.5% and was recorded for subtype A/Cambodia/e0826360/2020(H3N2), the dominant type causing infections in the epidemic season 2021/2022 confirmed by molecular biology methods. Geometric mean titer (GMT) values and protective levels for B/Washington/02/2019 (B/Victoria lineage) antigen were higher for men than women (respectively 38.4 vs 67.6; P<0.001 and 58.0% vs 74.6%; P<0.001). The protective levels of antibodies among patients vaccinated vs unvaccinated against COVID-19 were higher for B/Washington/02/2019 (B/Victoria lineage) and B/Phuket/3073/2013 (B/Yamagata lineage) antigens (64.2% vs 44.4%; P=0.023 and 78.6% vs 55.6%; P=0.004). GMT values for vaccinated against COVID-19 were also higher. There were no significant differences between younger (65-79 years) and older (≥80 years) seniors. CONCLUSIONS The analysis shows differences in the level of individual antibodies, GMT and the protective level depending on subtypes of influenza A or B virus, B/Victoria or B/Yamagata lineage, sex, and previous vaccination history against influenza and COVID-19.
Asunto(s)
Anticuerpos Antivirales , COVID-19 , Vacunas contra la Influenza , Gripe Humana , SARS-CoV-2 , Humanos , Anciano , Polonia/epidemiología , Masculino , Femenino , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Gripe Humana/prevención & control , Gripe Humana/inmunología , Gripe Humana/epidemiología , Vacunas contra la Influenza/inmunología , Anciano de 80 o más Años , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/epidemiología , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Factores Sexuales , Vacunación , Subtipo H3N2 del Virus de la Influenza A/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Factores de Edad , Subtipo H1N1 del Virus de la Influenza A/inmunología , Pruebas de Inhibición de Hemaglutinación/métodos , Estaciones del AñoRESUMEN
Background: Concomitant administration of COVID-19, influenza, and pneumococcal vaccines could reduce the burden on healthcare systems. However, the immunogenicity and safety of various combinations of a third booster dose of SARS-CoV-2 inactivated vaccine (CoronaVac), inactivated quadrivalent influenza vaccine (IIV4), and 23-valent pneumococcal polysaccharide vaccine (PPV23), particularly in different age groups, is still unknown. Methods: A phase 4, randomized, open-label, controlled trial was conducted in Beijing, China. 636 healthy adults were divided into two age groups (18-59 and ≥60 years) and randomized equally into three groups: CoronaVac and IIV4 followed by PPV23; CoronaVac and PPV23 followed by IIV4; or CoronaVac followed by IIV4 and PPV23, with a 28-day interval between vaccinations. Immunogenicity was evaluated by measuring antibody titers, and safety was monitored. ClinicalTrials.gov Identifier: NCT05298800. Results: Co-administration of a third dose of CoronaVac, IIV4, and PPV23 in any combination was safe. Among adults aged 18-59, co-administration with PPV23 maintained non-inferiority of antibody levels for CoronaVac and IIV4, despite a slight reduction in antibody responses. This reduction was not observed in participants ≥60 years. Furthermore, co-administration of IIV4 and PPV23 affected seroconversion rates for both vaccines. Conclusions: Co-administration of the third dose of SARS-CoV-2 inactivated vaccine with the influenza vaccine, followed by PPV23, may be optimal for adults aged 18-59. In adults ≥60, all vaccine combinations were immunogenic, suggesting a flexible vaccination approach. Since antibody measurements were taken 28 days post-vaccination, ongoing surveillance is essential to assess the longevity of the immune responses.
Asunto(s)
Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , Inmunogenicidad Vacunal , Vacunas contra la Influenza , Vacunas Neumococicas , SARS-CoV-2 , Humanos , Persona de Mediana Edad , Vacunas Neumococicas/inmunología , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/efectos adversos , Masculino , Femenino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , Adulto , COVID-19/prevención & control , COVID-19/inmunología , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/efectos adversos , Vacunas contra la Influenza/administración & dosificación , Anciano , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Adulto Joven , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/efectos adversos , Adolescente , China , Gripe Humana/prevención & control , Gripe Humana/inmunologíaRESUMEN
Recombinant influenza virus neuraminidase (NA) is a promising broadly protective influenza vaccine candidate. However, the recombinant protein alone is not sufficient to induce durable and protective immune responses and requires the coadministration of immunostimulatory molecules. Here, we evaluated the immunogenicity and cross-protective potential of a recombinant influenza virus N2 neuraminidase vaccine construct, adjuvanted with a toll-like receptor 9 (TLR9) agonist (CpG 1018® adjuvant), and alum. The combination of CpG 1018 adjuvant and alum induced a balanced and robust humoral and T-cellular immune response against the NA, which provided protection and reduced morbidity against homologous and heterologous viral challenges in mouse and hamster models. This study supports Syrian hamsters as a useful complementary animal model to mice for pre-clinical evaluation of influenza virus vaccines.
Asunto(s)
Adyuvantes Inmunológicos , Anticuerpos Antivirales , Vacunas contra la Influenza , Neuraminidasa , Infecciones por Orthomyxoviridae , Animales , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Neuraminidasa/inmunología , Neuraminidasa/genética , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/inmunología , Ratones , Adyuvantes Inmunológicos/administración & dosificación , Femenino , Cricetinae , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Adyuvantes de Vacunas , Ratones Endogámicos BALB C , Protección Cruzada/inmunología , Mesocricetus , Oligodesoxirribonucleótidos/administración & dosificación , Oligodesoxirribonucleótidos/inmunología , Compuestos de Alumbre/administración & dosificación , Modelos Animales de Enfermedad , Inmunidad CelularRESUMEN
BACKGROUND: Influenza B/Yamagata viruses exhibited weak antigenic selection in recent years, reducing their prevalence over time and requiring no update of the vaccine component since 2015. To date, no B/Yamagata viruses have been isolated or sequenced since March 2020. METHODS: The antibody prevalence against the current B/Yamagata vaccine strain in Italy was investigated: For each influenza season from 2012/2013 to 2021/2022, 100 human serum samples were tested by haemagglutination inhibition (HAI) assay against the vaccine strain B/Phuket/3073/2013. In addition, the sequences of 156 B/Yamagata strains isolated during the influenza surveillance activities were selected for analysis of the haemagglutinin genome segment. RESULTS: About 61.9% of the human samples showed HAI antibodies, and 21.7% had protective antibody levels. The prevalence of antibodies at protective levels in the seasons between the isolation of the strain and its inclusion in the vaccine was between 11% and 25%, with no significant changes observed in subsequent years. A significant increase was observed in the 2020/2021 season, in line with the increase in influenza vaccine uptake during the pandemic. Sequence analysis showed that from 2014/2015 season onward, all B/Yamagata strains circulating in Italy were closely related to the B/Phuket/2013 vaccine strain, showing only limited amino acid variation. CONCLUSIONS: A consistent prevalence of antibodies to the current B/Yamagata vaccine strain in the general population was observed. The prolonged use of a well-matched influenza vaccine and a low antigenic diversity of B/Yamagata viruses may have facilitated a strong reduction in B/Yamagata circulation, potentially contributing to the disappearance of this lineage.
Asunto(s)
Anticuerpos Antivirales , Pruebas de Inhibición de Hemaglutinación , Virus de la Influenza B , Vacunas contra la Influenza , Gripe Humana , Italia/epidemiología , Humanos , Virus de la Influenza B/genética , Virus de la Influenza B/clasificación , Virus de la Influenza B/aislamiento & purificación , Virus de la Influenza B/inmunología , Gripe Humana/epidemiología , Gripe Humana/virología , Anticuerpos Antivirales/sangre , Prevalencia , Vacunas contra la Influenza/inmunología , Estaciones del Año , Filogenia , Persona de Mediana Edad , Femenino , Adulto , Masculino , Adolescente , Adulto Joven , Niño , Anciano , PreescolarRESUMEN
Vaccination is crucial for the prevention and mitigation of avian influenza infections in China. The inactivated H7N9 vaccine, when administered to poultry, significantly lowers the risk of infection among both poultry and humans, while also markedly decreasing the prevalence of H7N9 detections. Highly pathogenic (HP) H7N9 viruses occasionally appear, whereas their low pathogenicity (LP) counterparts have been scarcely detected since 2018. However, these contributing factors remain poorly understood. We conducted an exploratory investigation of the mechanics via the application of comprehensive bioinformatic approaches. We delineated the Yangtze River Delta (YRD) H7N9 lineage into 5 clades (YRD-A to E). Our findings highlight the emergence and peak occurrence of the LP H7N9-containing YRD-E clade during the 5th epidemic wave in China's primary poultry farming areas. A more effective control of LP H7N9 through vaccination was observed compared to that of its HP H7N9 counterpart. YRD-E exhibited a tardy evolutionary trajectory, denoted by the conservation of its genetic and antigenic variation. Our analysis of YRD-E revealed only minimal amino acid substitutions along its phylogenetic tree and a few selective sweep mutations since 2016. In terms of epidemic fitness, the YRD-E was measured to be lower than that of the HP variants. Collectively, these findings underscore the conserved evolutionary patterns distinguishing the YRD-E. Given the conservation presented in its evolutionary patterns, the YRD-E LP H7N9 is hypothesized to be associated with a reduction following the mass vaccination in a relatively short period owing to its lower probability of antigenic variation that might affect vaccine efficiency.
Asunto(s)
Evolución Molecular , Subtipo H7N9 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Aviar , Filogenia , Aves de Corral , Subtipo H7N9 del Virus de la Influenza A/genética , Subtipo H7N9 del Virus de la Influenza A/inmunología , Subtipo H7N9 del Virus de la Influenza A/clasificación , Subtipo H7N9 del Virus de la Influenza A/patogenicidad , Animales , Gripe Aviar/virología , Gripe Aviar/prevención & control , China/epidemiología , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/genética , Aves de Corral/virología , Vacunación Masiva , Gripe Humana/prevención & control , Gripe Humana/virología , Gripe Humana/epidemiología , Enfermedades de las Aves de Corral/virología , Enfermedades de las Aves de Corral/prevención & control , Humanos , Pollos/virología , Variación Antigénica/genéticaRESUMEN
Early-life nutrition significantly impacts vaccination efficacy in infants, whose immune response to vaccines is weaker compared to adults. This study investigated vaccination efficacy in female C57Bl/6JOlaHsd mice (6 weeks old) fed diets with 0.7% galacto-oligosaccharides (GOS)/long-chain fructo-oligosaccharides (lcFOS) (9:1), 0.3% human milk oligosaccharides (HMOS), or a combination (GFH) for 14 days prior to and during vaccination. Delayed-type hypersensitivity (DTH) was measured by assessing ear swelling following an intradermal challenge. Influvac-specific IgG1 and IgG2a levels were assessed using ELISAs, while splenic T and B lymphocytes were analyzed for frequency and activation via flow cytometry. Additionally, cytokine production was evaluated using murine splenocytes co-cultured with influenza-loaded dendritic cells. Mice on the GFH diet showed a significantly enhanced DTH response (p < 0.05), increased serological IgG1 levels, and a significant rise in memory B lymphocytes (CD27+ B220+ CD19+). GFH-fed mice also exhibited more activated splenic Th1 cells (CD69+ CXCR3+ CD4+) and higher IFN-γ production after ex vivo restimulation (p < 0.05). These findings suggest that GOS/lcFOS and HMOS, particularly in combination, enhance vaccine responses by improving memory B cells, IgG production, and Th1 cell activation, supporting the potential use of these prebiotics in infant formula for better early-life immune development.
Asunto(s)
Vacunas contra la Influenza , Ratones Endogámicos C57BL , Leche Humana , Oligosacáridos , Animales , Oligosacáridos/farmacología , Leche Humana/inmunología , Leche Humana/química , Femenino , Vacunas contra la Influenza/inmunología , Humanos , Ratones , Vacunación , Inmunoglobulina G/sangre , Galactosa , Linfocitos B/inmunología , Bazo/inmunología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Anticuerpos Antivirales/sangreRESUMEN
Seasonal influenza is a severe disease that significantly impacts public health, causing millions of infections and hundreds of thousands of deaths each year. Seasonal influenza viruses, particularly the H3N2 subtype, exhibit high antigenic variability, often leading to mismatch between vaccine strains and circulating strains. Therefore, rapidly assessing the alignment between existing seasonal influenza vaccine and circulating strains is crucial for enhancing vaccine efficacy. This study, based on a pseudovirus platform, evaluated the match between current influenza H3N2 vaccine strains and circulating strains through cross-neutralization assays using clinical human immune sera against globally circulating influenza virus strains. The research results show that although mutations are present in the circulating strains, the current H3N2 vaccine strain still imparting effective protection, providing a scientific basis for encouraging influenza vaccination. This research methodology can be sustainably applied for the neutralization potency assessment of subsequent circulating strains, establishing a persistent methodological framework.
Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Subtipo H3N2 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Pruebas de Neutralización , Subtipo H3N2 del Virus de la Influenza A/inmunología , Humanos , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Gripe Humana/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Estaciones del Año , Variación Antigénica , Adulto , Eficacia de las Vacunas , Adulto JovenRESUMEN
In the post-COVID-19 pandemic era, influenza virus infections continuously lead to a global disease burden. Evaluating vaccine effectiveness against influenza infection is crucial to inform vaccine design and vaccination strategy. In this study, we recruited 1120 patients with influenza-like illness (ILI) who attended fever clinics of 4 sentinel hospitals in the Ili Kazakh Autonomous Prefecture, Xinjiang Uygur Autonomous Region, China, from January 1 to April 7, 2024. Using a test-negative design, we estimated influenza vaccine effectiveness (VE) of 54.7% (95% CrI: 23.7, 73.1) against medical-attended influenza infection, with 62.3% (95% CrI: 29.3, 79.8) against influenza A, and 51.2% (95% CrI: 28.7, 83.0) against influenza B. Despite the moderate VE estimated in this study, influenza vaccination remains the most important approach to prevent influenza at the community level.
Asunto(s)
Vacunas contra la Influenza , Gripe Humana , Eficacia de las Vacunas , Humanos , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , China/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios de Casos y Controles , Adolescente , Anciano , Adulto Joven , Niño , Vacunación/estadística & datos numéricos , Preescolar , Estaciones del Año , Virus de la Influenza B/inmunología , COVID-19/prevención & control , COVID-19/epidemiología , COVID-19/inmunología , Lactante , Virus de la Influenza A/inmunologíaRESUMEN
BACKGROUND: Influenza viruses pose a persistent threat to global public health, necessitating the development of innovative and broadly effective vaccines. METHODS: This study focuses on a multiepitope vaccine (MEV) designed to provide broad-spectrum protection against different influenza viruses. The MEV, containing 19 B-cell linear epitopes, 7 CD4+ T cells, and 11 CD8+ T cells epitopes identified through enzyme-linked immunospot assay (ELISPOT) in influenza viruses infected mice, was administered through a regimen of two doses of DNA vaccine followed by one dose of a protein vaccine in C57BL/6 female mice. FINDINGS: Upon lethal challenge with both seasonal circulating strains (H1N1, H3N2, BV, and BY) and historical strains (H1N1-PR8 and H3N2-X31), MEV demonstrated substantial protection against different influenza seasonal strains, with partial efficacy against historical strains. Notably, the increased germinal centre B cells and antibody-secreting cells, along with robust T cell immune responses, highlighted the comprehensive immune defence elicited by MEV. Elevated hemagglutinin inhibition antibody was also observed against seasonal circulating and historical strains. Additionally, mice vaccinated with MEV exhibited significantly lower counts of inflammatory cells in the lungs compared to negative control groups. INTERPRETATION: Our results demonstrated the efficacy of a broad-spectrum MEV against influenza viruses in mice. Conducting long-term studies to evaluate the durability of MEV-induced immune responses and explore its potential application in diverse populations will offer valuable insights for the continued advancement of this promising vaccine. FUNDING: Funding bodies are described in the Acknowledgments section.
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Epítopos de Linfocito B , Virus de la Influenza B , Vacunas contra la Influenza , Infecciones por Orthomyxoviridae , Animales , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Ratones , Virus de la Influenza B/inmunología , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/inmunología , Femenino , Epítopos de Linfocito B/inmunología , Virus de la Influenza A/inmunología , Anticuerpos Antivirales/inmunología , Epítopos de Linfocito T/inmunología , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Vacunas de ADN/inmunología , Vacunas de ADN/administración & dosificación , Estaciones del Año , Subtipo H3N2 del Virus de la Influenza A/inmunología , HumanosRESUMEN
During the coronavirus disease 2019 (COVID-19) pandemic, scheduled vaccinations were postponed, mass vaccination programmes were suspended and opportunities for healthcare workers to administer vaccines ad hoc decreased. The aims of this systematic literature review were to determine the impact of the COVID-19 pandemic on vaccine confidence, intent and uptake in preexisting routine childhood or adult vaccination programmes, and to identify factors associated with changes in acceptance, intent and uptake of preexisting vaccines. Medline and Embase were searched for studies in Australia, Brazil, Canada, China, Japan, the USA, and European countries, published between 1 January 2021 and 4 August 2022. A complementary gray literature search was conducted between 11 and 13 October 2022, and supplemented with additional gray research in October 2023. In total, 54 citations were included in the review. Study design and geography were heterogeneous. The number of adults who received or intended to receive an influenza or pneumococcal vaccine was higher during the pandemic than in previous seasons (n = 28 studies). In addition, increased acceptance of adult vaccinations was observed during 2020-21 compared with 2019-20 (n = 12 studies). The rates of childhood vaccinations decreased during the COVID-19 pandemic across several countries (n = 11 studies). Factors associated with changes in intention to receive a vaccination, or uptake of influenza vaccine, included previous vaccination, older age, higher perceived risk of contracting COVID-19, anxiety regarding the pandemic and fear of contracting COVID-19. Acceptance and uptake of influenza and pneumococcal vaccines generally increased after onset of the COVID-19 pandemic.
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COVID-19 , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Vacunación/psicología , Vacunación/estadística & datos numéricos , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , Adulto , Vacunas contra la Influenza/administración & dosificación , Vacunas contra la Influenza/inmunología , Programas de Inmunización , Niño , SARS-CoV-2/inmunología , Vacilación a la Vacunación/estadística & datos numéricos , Vacilación a la Vacunación/psicología , Vacunas Neumococicas/administración & dosificación , Pandemias/prevención & control , Aceptación de la Atención de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/psicologíaRESUMEN
Avian influenza virus has been long considered the main threat for a future pandemic. Among the possible avian influenza virus subtypes, A(H5N1) clade 2.3.4.4b is becoming enzootic in mammals, representing an alarming step towards a pandemic. In particular, genotype B3.13 has recently caused an outbreak in US dairy cattle. Since pandemic preparedness is largely based on the availability of prepandemic candidate vaccine viruses, in this review we will summarize the current status of the enzootics, and challenges for H5 vaccine manufacturing and delivery.
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Subtipo H5N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Aviar , Animales , Vacunas contra la Influenza/inmunología , Humanos , Subtipo H5N1 del Virus de la Influenza A/inmunología , Subtipo H5N1 del Virus de la Influenza A/genética , Gripe Aviar/prevención & control , Gripe Aviar/virología , Gripe Aviar/epidemiología , Gripe Humana/prevención & control , Gripe Humana/epidemiología , Gripe Humana/inmunología , Gripe Humana/virología , Aves/virología , Pandemias/prevención & controlAsunto(s)
Vacunas contra la Influenza , Gripe Humana , Desarrollo de Vacunas , Vacunas contra la Influenza/inmunología , Humanos , Gripe Humana/prevención & control , Gripe Humana/inmunología , Gripe Humana/virología , Orthomyxoviridae/inmunología , Animales , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virologíaRESUMEN
Vaccine responsiveness is often reduced in older adults. Yet, our lack of understanding of low vaccine responsiveness hampers the development of effective vaccination strategies to reduce the impact of infectious diseases in the ageing population. Young-adult (25-49 y), middle-aged (50-64 y) and older-adult ( ≥ 65 y) participants of the VITAL clinical trials (n = 315, age-range: 28-98 y), were vaccinated with an annual (2019-2020) quadrivalent influenza (QIV) booster vaccine, followed by a primary 13-valent pneumococcal-conjugate (PCV13) vaccine (summer/autumn 2020) and a primary series of two SARS-CoV-2 mRNA-1273 vaccines (spring 2021). This unique setup allowed investigation of humoral responsiveness towards multiple vaccines within the same individuals over the adult age-range. Booster QIV vaccination induced comparable H3N2 hemagglutination inhibition (HI) titers in all age groups, whereas primary PCV13 and mRNA-1273 vaccination induced lower antibody concentrations in older as compared to younger adults (primary endpoint). The persistence of humoral responses, towards the 6 months timepoint, was shorter in older adults for all vaccines (secondary endpoint). Interestingly, highly variable vaccine responder profiles overarching multiple vaccines were observed. Yet, approximately 10% of participants, mainly comprising of older male adults, were classified as low responders to multiple vaccines. This study aids the identification of risk groups for low vaccine responsiveness and hence supports targeted vaccination strategies. Trial number: NL69701.041.19, EudraCT: 2019-000836-24.
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Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Antivirales , COVID-19 , Inmunidad Humoral , Inmunización Secundaria , Vacunas contra la Influenza , Gripe Humana , Vacunas Neumococicas , SARS-CoV-2 , Humanos , Persona de Mediana Edad , Adulto , Anciano , Masculino , Femenino , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Inmunidad Humoral/inmunología , Vacunas Neumococicas/inmunología , Vacunas Neumococicas/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , SARS-CoV-2/inmunología , Anciano de 80 o más Años , Vacuna nCoV-2019 mRNA-1273/inmunología , Gripe Humana/prevención & control , Gripe Humana/inmunología , Factores de Edad , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Subtipo H3N2 del Virus de la Influenza A/inmunología , Vacunación , Pruebas de Inhibición de HemaglutinaciónRESUMEN
The differentiation and specificity of human CD4+ T follicular helper cells (TFH cells) after influenza vaccination have been poorly defined. Here we profiled blood and draining lymph node (LN) samples from human volunteers for over 2 years after two influenza vaccines were administered 1 year apart to define the evolution of the CD4+ TFH cell response. The first vaccination induced an increase in the frequency of circulating TFH (cTFH) and LN TFH cells at week 1 postvaccination. This increase was transient for cTFH cells, whereas the LN TFH cells further expanded during week 2 and remained elevated in frequency for at least 3 months. We observed several distinct subsets of TFH cells in the LN, including pre-TFH cells, memory TFH cells, germinal center (GC) TFH cells and interleukin-10+ TFH cell subsets beginning at baseline and at all time points postvaccination. The shift toward a GC TFH cell phenotype occurred with faster kinetics after the second vaccine compared to the first vaccine. We identified several influenza-specific TFH cell clonal lineages, including multiple responses targeting internal influenza virus proteins, and found that each TFH cell state was attainable within a clonal lineage. Thus, human TFH cells form a durable and dynamic multitissue network.
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Diferenciación Celular , Centro Germinal , Vacunas contra la Influenza , Gripe Humana , Células T Auxiliares Foliculares , Vacunación , Humanos , Vacunas contra la Influenza/inmunología , Células T Auxiliares Foliculares/inmunología , Gripe Humana/inmunología , Gripe Humana/prevención & control , Centro Germinal/inmunología , Diferenciación Celular/inmunología , Ganglios Linfáticos/inmunología , Adulto , Femenino , Masculino , Persona de Mediana Edad , Interleucina-10/inmunología , Interleucina-10/metabolismo , Memoria Inmunológica/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Adulto JovenRESUMEN
Influenza still poses a significant challenge due to its high mutation rates and the low effectiveness of traditional vaccines. At present, antibodies that neutralize the highly variable hemagglutinin antigen are a major driver of the observed variable protection. To decipher how influenza vaccines can be improved, an analysis of licensed vaccine platforms was conducted, contrasting the strengths and limitations of their different mechanisms of protection. Through this review, it is evident that these vaccines do not elicit the robust cellular immune response critical for protecting high-risk groups. Emerging platforms, such as RNA vaccines, that induce robust cellular responses that may be additive to the recognized mechanism of protection through hemagglutinin inhibition may overcome these constraints to provide broader, protective immunity. By combining both humoral and cellular responses, such platforms could help guide the future influenza vaccine development.
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Vacunas contra la Influenza , Gripe Humana , Humanos , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Gripe Humana/prevención & control , Gripe Humana/inmunología , Animales , Inmunidad Celular/inmunología , Vacunación/métodos , Desarrollo de Vacunas/métodos , Inmunidad Humoral/inmunologíaRESUMEN
Influenza virus infection poses a continual menace to public health. Here, we developed soluble trimeric HA ectodomain vaccines by establishing interprotomer disulfide bonds in the stem region, which effectively preserve the native antigenicity of stem epitopes. The stable trimeric H1 ectodomain proteins exhibited higher thermal stabilities in comparison with unmodified HAs and showed strong binding activities towards a panel of anti-stem cross-reactive antibodies that recognize either interprotomer or intraprotomer epitopes. Negative stain transmission electron microscopy (TEM) analysis revealed the stable trimer architecture of the interprotomer disulfide-stapled WA11#5, NC99#2, and FLD#1 proteins as well as the irregular aggregation of unmodified HA molecules. Immunizations of mice with those trimeric HA ectodomain vaccines formulated with incomplete Freund's adjuvant elicited significantly more potent cross-neutralizing antibody responses and offered broader immuno-protection against lethal infections with heterologous influenza strains compared to unmodified HA proteins. Additionally, the findings of our study indicate that elevated levels of HA stem-specific antibody responses correlate with strengthened cross-protections. Our design strategy has proven effective in trimerizing HA ectodomains derived from both influenza A and B viruses, thereby providing a valuable reference for designing future influenza HA immunogens.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Disulfuros , Glicoproteínas Hemaglutininas del Virus de la Influenza , Vacunas contra la Influenza , Ratones Endogámicos BALB C , Infecciones por Orthomyxoviridae , Animales , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Anticuerpos Antivirales/inmunología , Ratones , Disulfuros/química , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología , Anticuerpos Neutralizantes/inmunología , Femenino , Protección Cruzada/inmunología , Reacciones Cruzadas , Humanos , Gripe Humana/prevención & control , Gripe Humana/inmunología , Gripe Humana/virología , Epítopos/inmunología , Epítopos/genética , Epítopos/química , Multimerización de Proteína , Virus de la Influenza B/inmunología , Virus de la Influenza B/genética , Virus de la Influenza B/químicaRESUMEN
OBJECTIVES: This study was to assess the lot-to-lot consistency, immunogenicity and safety of three manufacturing lots of a quadrivalent inactivated influenza vaccine (IIV4). METHODS: A randomized, double-blind, phase IV clinical trial was conducted in healthy children, adolescents and adults aged 9-59 years in Guizhou Province, China. Eligible participants were enrolled and randomized into three groups in a ratio of 1:1:1 to receive a single dose of one of three manufacturing lots of IIV4. Serum samples were collected before and 28 days after vaccination for hemagglutination inhibition (HI) antibody testing. Safety data were collected for up to 28 days after vaccination. The primary objective was to evaluate the lot-to-lot consistency of immune response as assessed by the geometric mean titer (GMT) of HI antibody at 28 days after vaccination. RESULTS: Between November 27, 2022 and December 18, 2022, 1260 eligible participants were enrolled, with similar participant demographics among groups. Immune responses after vaccination were comparable across groups, with the 95% confidence intervals (CIs) of GMT ratios for all 4 strains falling into the equivalence criterion of (0.67, 1.5). The seroconversion rates (SCRs) and seroprotection rates (SPRs) met the US Center or Biologics Evaluation and Research (CBER) criteria for all strains for each lot (lower limit of 95% CI of SCR ≥ 40% and SPR ≥ 70%). The incidences of solicited and unsolicited adverse reactions were similar among three groups, most of which (91.9%) were mild or moderate in severity. A total of 11 serious adverse events were reported during the study, and all were considered unrelated to vaccination. CONCLUSION: The three manufacturing lots of IIV4 demonstrated consistent immunogenicity. IIV4 can elicit satisfactory immune responses for all four strains and no safety concerns were identified. CLINICAL TRIAL REGISTRATION: Identifier No. NCT05512494.