Search bioRxivSearch

Biology subjects

Balmaseda, A.

Publications and source records attributed to Balmaseda, A..

3 recordsLinked to original sources

The respiratory microbiome and susceptibility to influenza virus infection

Influenza is a major cause of morbidity and mortality worldwide. However, vaccine effectiveness has been low to moderate in recent years and vaccine coverage remains low, especially in low- and middle-income countries. Supplementary methods of prevention should be explored to reduce the high burden of influenza.\n\nA potential target is the respiratory tract microbiome, complex microbial communities which envelop the respiratory epithelium and play an important role in shaping host immunity. Using a household transmission study, we examined whether the nose/throat microbiota was associated with influenza susceptibility among participants exposed to influenza virus in the household. Further, we characterized changes in the nose/throat microbiota to explore whether community stability was influenced by influenza virus infection.\n\nUsing a generalized linear mixed effects model, we found a bacterial community type associated with decreased susceptibility to influenza. The community type was rare and transitory among young children but a prevalent and stable community type among adults. Using boosting and linear mixed effects models, we found associations between the nose/throat microbiota and influenza also existed at the taxa level, specifically with the relative abundance of Alloprevotella, Prevotella, and Bacteroides oligotypes.\n\nWe found high rates of change in the bacterial community among both secondary cases and household contacts who were not infected during follow up. Preliminary results suggest short-term changes in the bacterial community structure may differ between the two groups, but further work is needed to validate our observations.\n\nLastly, age was strongly associated with susceptibility to influenza and the nose/throat bacterial community structure. Although additional studies are needed to determine causality, our results suggest the nose/throat microbiome may be a potential target for reducing the burden of influenza.\n\nAuthor summaryMicrobiome research has transformed our understanding of microbes and human health. Resident bacteria can protect the host from pathogens by shaping immunological responses. These new insights suggest the microbiome could be a target for preventing influenza virus infection, a major cause of illness and death worldwide. In this study, we explored the relationship between the nose/throat microbiota and influenza virus in Nicaraguan households.\n\nHousehold members were enrolled immediately after one member was diagnosed with influenza virus infection. This study design allowed us to identify associations between the microbiota and influenza susceptibility. We also explored whether influenza virus infection altered the bacterial community structure and found short-term changes were common among both secondary cases and household members who remained influenza negative during follow up. Lastly, we found age played major roles in both influenza susceptibility and in short-terms changes in the microbiota. Although much work is needed to determine causal relationships, our findings suggest strategies that appropriately modify the microbiome might be useful in preventing influenza virus infections.

epidemiology

Early transcriptional responses after dengue vaccination mirror the response to natural infection and predict neutralizing antibody titers

BackgroundSeveral promising live attenuated virus (LAV) dengue vaccines are in development, but information about innate immune responses and early correlates of protection are lacking.\n\nMethodsWe characterized human genome-wide transcripts in whole blood from 10 volunteers at 11 time-points after immunization with the dengue virus type 3 (DENV-3) component of the NIH dengue vaccine candidate TV003 and from 30 hospitalized children with acute primary DENV-3 infection. We compared day-specific gene expression patterns with subsequent neutralizing antibody (NAb) titers.\n\nResultsThe transcriptional response to vaccination was largely confined to days 5-20 and was dominated by an interferon-associated signature and a cell cycle signature that peaked on days 8 and 14, respectively. Changes in transcript abundance were much greater in magnitude and scope in symptomatic natural infection than following vaccination (maximum fold-change >200 versus 21 post-vaccination; 3,210 versus 286 transcripts with significant fold-change), but shared gene modules were induced in the same sequence. The abundance of 131 transcripts on days 8 and 9 post-vaccination was strongly correlated with NAb titers measured 6 weeks post-vaccination.\n\nConclusionsLAV dengue vaccination elicits early transcriptional responses that mirror those found in symptomatic natural infection and provide candidate early markers of protection against DENV infection.\n\nClinical Trial Registration Number: NCT00831012 (available at clinicaltrials.gov)\n\nSummary: Interferon- and cell cycle-associated gene transcript abundance levels in the peripheral blood of dengue vaccine recipients on days 8 and 9 post-vaccination were associated with dengue neutralizing antibody titers on day 42, and mirrored responses in primary dengue infection, suggesting the possibility of predicting protective immunity.

immunology

Capturing diverse microbial sequence with comprehensive and scalable probe design

Metagenomic sequencing has the potential to transform microbial detection and characteri zation, but new tools are needed to improve its sensitivity. We developed CATCH (Compact Aggregation of Targets for Comprehensive Hybridization), a computational method to enhance nucleic acid capture for enrichment of diverse microbial taxa. CATCH designs compact probe sets that achieve full coverage of known sequence diversity and that scale well with this diversity. To illustrate applications of CATCH, we focused on capturing viral genomes. We designed, synthesized, and validated multiple probe sets, including one that targets whole genomes of the 356 viral species known to infect humans. Capture with these probe sets enriched unique viral content on average 18x and allowed us to assemble genomes that we could not otherwise recover, while accurately preserving within-sample diversity. We used this approach to recover genomes from the 2018 Lassa fever outbreak in Nigeria and to improve detection of viral infections in samples with unknown content. Together, this work demonstrates a path toward more sensitive, cost-effective metagenomic sequencing.

genomics