RESUMO
T follicular helper (Tfh) cells are required to develop germinal center (GC) responses and drive immunoglobulin class switch, affinity maturation, and long-term B cell memory. In this study, we characterize a recently developed vaccine platform, nucleoside-modified, purified mRNA encapsulated in lipid nanoparticles (mRNA-LNPs), that induces high levels of Tfh and GC B cells. Intradermal vaccination with nucleoside-modified mRNA-LNPs encoding various viral surface antigens elicited polyfunctional, antigen-specific, CD4+ T cell responses and potent neutralizing antibody responses in mice and nonhuman primates. Importantly, the strong antigen-specific Tfh cell response and high numbers of GC B cells and plasma cells were associated with long-lived and high-affinity neutralizing antibodies and durable protection. Comparative studies demonstrated that nucleoside-modified mRNA-LNP vaccines outperformed adjuvanted protein and inactivated virus vaccines and pathogen infection. The incorporation of noninflammatory, modified nucleosides in the mRNA is required for the production of large amounts of antigen and for robust immune responses.
Assuntos
Linfócitos B/imunologia , Centro Germinativo/citologia , Nucleosídeos/metabolismo , RNA Mensageiro/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Adjuvantes Imunológicos/farmacologia , Animais , Anticorpos Neutralizantes/imunologia , Formação de Anticorpos/imunologia , Antígenos/metabolismo , Lipídeos/química , Macaca mulatta , Nanopartículas/química , Subunidades Proteicas/metabolismo , Fatores de Tempo , VacinaçãoRESUMO
INTRODUCTION: Previous evidence linked low socioeconomic status with higher smoking prevalence. Our objective was to assess the strength of this association in the world population, updating a previous work. METHODS: Systematic review and meta-analysis of observational studies. Subgroup analyses included continents, WHO regions, country mortality levels, gender, age, risk of bias, and study publication date. Independent reviewers selected studies, assessed potential bias and extracted data. We searched MEDLINE, EMBASE, CENTRAL, SOCINDEX, AFRICAN INDEX MEDICUS, and LILACS, and other sources from 1989 to 2013 reporting direct measurements of income and current cigarette smoking. RESULTS: We retrieved 13,583 articles and included 93 for meta-analysis. Median smoking prevalence was 17.8% (range 3-70%). Lower income was consistently associated with higher smoking prevalence (odds ratio [OR]: 1.45; 95% confidence interval [CI]: 1.35-1.56). This association was statistically significant in the subgroup analysis by WHO regions for the Americas (OR: 1.54; 95% CI: 1.42-1.68), South East Asia (OR: 1.53; 95% CI: 1.10-2.00), Europe (OR: 1.45; 95% CI: 1.29-1.63), and Western Pacific (OR: 1.32; 95% CI: 1.02-1.72), and in studies conducted during 1990s (OR: 1.42; 95% CI: 1.24-1.62) and 2000s (OR: 1.48; 95%CI: 1.30-1.64). Likewise, it was noted in low-mortality countries (OR: 1.48; 95% CI: 1.37-1.60) and for both genders. Prevalence was highest in the lowest income levels compared to the middle (OR: 1.69; 95% CI: 1.49-1.92), followed by the middle level compared to the highest (OR: 1.31; 95% CI: 1.20-1.43). CONCLUSIONS: Our results show that current cigarette smoking was significantly associated with lower income worldwide and across subgroups, suggesting a dose-response relationship. IMPLICATIONS: This unique updated systematic review shows a consistent inverse dose-response relationship between cigarette smoking and income level, present among most geographical areas and country characteristics. Public health measures should take into account this potential inequity and consider special efforts directed to disadvantaged populations.
Assuntos
Fumar Cigarros/economia , Fumar Cigarros/epidemiologia , Renda , Adulto , América/epidemiologia , Sudeste Asiático/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto/métodos , Pobreza/economia , Prevalência , Classe Social , Populações VulneráveisRESUMO
Introduced disease has been implicated in recent wildlife extinctions and population declines worldwide. Both anthropogenic-induced change and natural environmental features can affect pathogen spread. Furthermore, environmental disturbance can result in changes in stress physiology, nutrition, and social structure, which in turn can suppress immune system function. However, it remains unknown whether landscape variation results in heterogeneity in host resistance to pathogens. Avian pox virus, a pathogen implicated in avian declines and extinctions in Hawaii, was introduced to the Galapagos in the 1890 s, and prevalence (total number of current infections) has increased recently in finches. We tested whether prevalence and recovery trends in 7 species of Galapagos finches varied by elevation or human land use. To do so, we used infection data obtained from 545 wild-caught birds. In addition, we determined whether annual changes in 4 aspects of innate immune function (complement protein activity, natural antibody activity, concentration of PIT54 protein, and heterophil:lymphocyte ratio) varied by elevation or land use. Prevalence and recovery rates did not vary by elevation from 2008 to 2009. Avian pox prevalence and proportion of recovered individuals in undeveloped and urban areas did not change from 2008 to 2009. In agricultural areas, avian pox prevalence increased 8-fold (from 2% to 17% of 234 individuals sampled) and proportion of recovered individuals increased (11% to 19%) from 2008 to 2009. These results suggest high disease-related mortality. Variation in immune function across human land-use types correlated with variation in both increased prevalence and susceptibility, which indicates changes in innate immune function may underlie changes in disease susceptibility. Our results suggest anthropogenic disturbance, in particular agricultural practices, may underlie immunological changes in host species that themselves contribute to pathogen emergence.