Influenza virus infection and aerosol shedding kinetics in a controlled human infection model DOI Creative Commons
Nishit Shetty, Meredith J. Shephard, Nicole C. Rockey

et al.

Journal of Virology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

ABSTRACT Establishing effective mitigation strategies to reduce the spread of influenza virus requires an improved understanding mechanisms transmission. We evaluated use a controlled human infection model using H3N2 seasonal study critical aspects transmission, including symptom progression and dynamics shedding. Eight volunteers were challenged with A/Perth/16/2009 (H3N2) between July September 2022 at Emory University Hospital. Viral shedding in nasopharynx, saliva, stool, urine, respiratory aerosols was monitored over quarantine period, symptoms tracked until day 15. In addition, environmental swabs collected from participant rooms examine fomite contamination, sera assess seroconversion by hemagglutination inhibition or microneutralization assays. Among eight participants, confirmed six (75%). Infectious viral RNA found multiple physiological compartments, fecal samples, aerosol particles, on surfaces immediate environment. Illness moderate, upper dominating. participants highest loads, antibody titers rose 15 post-inoculation, while low undetectable there little no increase functional titers. These data demonstrate safety utility features transmission manner will inform design future challenge studies focused modeling limiting CLINICAL TRIALS This is registered ClinicalTrials.gov as NCT05332899 . IMPORTANCE kinetics expand our knowledge help aimed human-to-human

Language: Английский

Sialylated IgG induces the transcription factor REST in alveolar macrophages to protect against lung inflammation and severe influenza disease DOI Creative Commons
Saborni Chakraborty, Bowie Yik-Ling Cheng,

Desmond L. Edwards

et al.

Immunity, Journal Year: 2024, Volume and Issue: 58(1), P. 182 - 196.e10

Published: Nov. 13, 2024

While most respiratory viral infections resolve with little harm to the host, severe symptoms arise when infection triggers an aberrant inflammatory response that damages lung tissue. Host regulators of virally induced inflammation have not been well defined. Here, we show enrichment for sialylated, but asialylated immunoglobulin G (IgG), predicted mild influenza disease in humans and was broadly protective against heterologous viruses a murine challenge model. Mechanistic studies sialylated IgG mediated this protection by inducing transcription factor repressor element-1 silencing (REST), which repressed nuclear κB (NF-κB)-driven responses, preventing protecting function during infection. Therapeutic administration recombinant, Fc molecule clinical development similarly activated REST protected disease, demonstrating pathway could be clinically harnessed. Overall, induction through signaling is strategy limit sequelae caused antigenically distinct strains.

Language: Английский

Citations

5
Influenza A virus in dairy cattle: infection biology and potential mammary gland-targeted vaccines DOI Creative Commons
Rodrigo Prado Martins, Daniel Marc, Pierre Germon

et al.

npj Vaccines, Journal Year: 2025, Volume and Issue: 10(1)

Published: Jan. 14, 2025

Abstract Influenza, a major “One Health” threat, has gained heightened attention following recent reports of highly pathogenic avian influenza in dairy cattle and cow-to-human transmission the USA. This review explores general aspects A virus (IAV) biology, its interactions with mammalian hosts, discusses key considerations for developing vaccines to prevent or curtail IAV infection bovine mammary gland spread through milk.

Language: Английский

Citations

0
State of the Art and Emerging Technologies in Vaccine Design for Respiratory Pathogens DOI
Matteo Ridelfi, Giulio Pierleoni, V. Fonseca

et al.

Seminars in Respiratory and Critical Care Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

Abstract In this review, we present the efforts made so far in developing effective solutions to prevent infections caused by seven major respiratory pathogens: influenza virus, syncytial virus (RSV), severe acute syndrome coronavirus 2 (SARS-CoV-2), Bordetella pertussis, Streptococcus pneumoniae (pneumococcus), Mycobacterium tuberculosis, and Pseudomonas aeruginosa. Advancements driven recent disease 2019 (COVID-19) crisis have largely focused on viruses, but prophylactic for bacterial pathogens are also needed, especially light of antimicrobial resistance (AMR) phenomenon. Here, discuss various innovative key technologies that can help address critical need, such as (a) development Lung-on-Chip ex vivo models gain a better understanding pathogenesis process host–microbe interactions; (b) more thorough investigation mechanisms behind mucosal immunity first line defense against pathogens; (c) identification correlates protection (CoPs) which, conjunction with Reverse Vaccinology 2.0 approach, push rational targeted design vaccines. By focusing these areas, expect substantial progress new vaccines pathogens, thereby enhancing global health framework increasingly concerning AMR emergence.

Language: Английский

Citations

0
Binding and neutralising antibodies to respiratory syncytial virus and influenza A virus in serum and bronchoalveolar lavage fluid of healthy adults in the United States: A cross-sectional study DOI Creative Commons

Amber I. Raja,

Ruth I. Connor, Alix Ashare

et al.

Vaccine, Journal Year: 2025, Volume and Issue: 53, P. 126936 - 126936

Published: March 3, 2025

Using serum and bronchoalveolar lavage (BAL) fluid collected from 20 healthy adults (23-37 years, 55 % female) in the United States, we measured immunoglobulin (Ig) A, IgG, neutralising activity against respiratory syncytial virus (RSV) influenza A (H1N1) virus. RSV-binding IgA IgG measurements were positively correlated with those BAL. For virus, BAL antibodies correlated, whereas did not show a significant correlation. RSV-specific (H1N1)-specific correlate between samples. These results demonstrate virus-specific correlations that may necessarily reflect functional activity. Further work is needed to confirm our preliminary observations, define immune correlates of these other viruses lower tract.

Language: Английский

Citations

0
Immunological drivers of zoonotic virus emergence, evolution, and endemicity DOI
Jyothi N. Purushotham, Holly L. Lutz, Edyth Parker

et al.

Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Deciphering immune responses: a comparative analysis of influenza vaccination platforms DOI Creative Commons
Charles H. Jones,

Teresa Hauguel,

Marie Beitelshees

et al.

Drug Discovery Today, Journal Year: 2024, Volume and Issue: 29(9), P. 104125 - 104125

Published: Aug. 2, 2024

Influenza still poses a significant challenge due to its high mutation rates and the low effectiveness of traditional vaccines. At present, antibodies that neutralize highly variable hemagglutinin antigen are major driver observed protection. To decipher how influenza vaccines can be improved, an analysis licensed vaccine platforms was conducted, contrasting strengths limitations their different mechanisms Through this review, it is evident these do not elicit robust cellular immune response critical for protecting high-risk groups. Emerging platforms, such as RNA vaccines, induce responses may additive recognized mechanism protection through inhibition overcome constraints provide broader, protective immunity. By combining both humoral responses, could help guide future development.

Language: Английский

Citations

2
Influenza Vaccine Effectiveness and Progress Towards a Universal Influenza Vaccine DOI Creative Commons
Benjamin J. Cowling,

George N. Okoli

Drugs, Journal Year: 2024, Volume and Issue: 84(9), P. 1013 - 1023

Published: Aug. 21, 2024

At various times in recent decades, surges have occurred optimism about the potential for universal influenza vaccines that provide strong, broad, and long-lasting protection could substantially reduce disease burden associated with seasonal epidemics as well threat posed by pandemic influenza. Each year more than 500 million doses of vaccine are administered around world, most being egg-grown inactivated subunit or split-virion vaccines. These tend to moderate effectiveness against medically attended A(H1N1) B, somewhat lower A(H3N2) where differences between strains circulating can occur frequently due antigenic drift egg adaptations strains. Several enhanced platforms been developed including cell-grown antigen, inclusion adjuvants, higher antigen doses, improve immunogenicity protection. During COVID-19 there was unprecedented speed development roll-out relatively new platforms, mRNA viral vector present opportunities beyond existing products. Other approaches continue be explored. Incremental improvements performance should achievable short medium term.

Language: Английский

Citations

2
Unravelling influenza correlates of protection: lessons from human A/H1N1 Challenge DOI Creative Commons
Rebecca Jane Cox,

Rishi D. Pathirana

mBio, Journal Year: 2024, Volume and Issue: 15(5)

Published: March 28, 2024

ABSTRACT Mucosal immunity is important in protecting from upper respiratory tract influenza infection. Human challenge provides a unique model to define correlates of protection with baseline immune responses being correlated the quantity and length viral shedding clinical outcomes. Here, we discuss recent work on mucosal systemic (R. Bean, L. T. Giurgea, A. Han, Czajkowski, et al., mBio 15:e02372-23, 2024, https://doi.org/10.1128/mbio.02372-23 ) place it context previous immunity. We also importance standardized assays allow global comparison relevant defining protection. Correlates are for designing next-generation broadly protective vaccines.

Language: Английский

Citations

1
Influenza virus infection and aerosol shedding kinetics in a controlled human infection model DOI Creative Commons
Nishit Shetty, Meredith J. Shephard, Nicole C. Rockey

et al.

Journal of Virology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

ABSTRACT Establishing effective mitigation strategies to reduce the spread of influenza virus requires an improved understanding mechanisms transmission. We evaluated use a controlled human infection model using H3N2 seasonal study critical aspects transmission, including symptom progression and dynamics shedding. Eight volunteers were challenged with A/Perth/16/2009 (H3N2) between July September 2022 at Emory University Hospital. Viral shedding in nasopharynx, saliva, stool, urine, respiratory aerosols was monitored over quarantine period, symptoms tracked until day 15. In addition, environmental swabs collected from participant rooms examine fomite contamination, sera assess seroconversion by hemagglutination inhibition or microneutralization assays. Among eight participants, confirmed six (75%). Infectious viral RNA found multiple physiological compartments, fecal samples, aerosol particles, on surfaces immediate environment. Illness moderate, upper dominating. participants highest loads, antibody titers rose 15 post-inoculation, while low undetectable there little no increase functional titers. These data demonstrate safety utility features transmission manner will inform design future challenge studies focused modeling limiting CLINICAL TRIALS This is registered ClinicalTrials.gov as NCT05332899 . IMPORTANCE kinetics expand our knowledge help aimed human-to-human

Language: Английский

Citations

1