Bacillus Calmette–Guérin-Induced Trained Immunity Is Not Protective for Experimental Influenza A/Anhui/1/2013 (H7N9) Infection in Mice

The combined protective effect of a polyphenol-rich extract, isolated from Geranium sanguineum L. (PC), and a novel naturally glycosylated Cu/Zn-containing superoxide dismutase, produced from the fungal strain Humicula lutea 103 (HL-SOD), in the experimental influenza A virus infection (EIVI) in mice, induced with the virus A/Aichi/2/68 (H3N2), was investigated. The combined application of HL-SOD and PC in doses, which by themselves do not defend significantly mice in EIVI, resulted in a synergistically increased protection, determined on the basis of protective indices and amelioration of lung injury. Lung weights and consolidation as well as infectious lung virus titers were all decreased significantly parallel to the reduction of the mortality rates; lung indices were raised. The excessive production of reactive oxygen species (ROS) by alveolar macrophages (aMØ) as well as the elevated levels of the lung antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), induced by EIVI, were brought to normal. For comparative reasons the combined protective effect of PC and vitamin C was investigated. The obtained results support the combined use of antioxidants for the treatment of influenza virus infection and in general indicate the beneficial protective role of combinations of viral inhibitors of natural origin with diverse modes of action.

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Mild Influenza A/H7N9 Infection Among Children in Guangdong Province

The Pediatric Infectious Disease Journal ◽

10.1097/inf.0000000000000492 ◽

2015 ◽

Vol 34 (1) ◽

pp. 104-107 ◽

Cited By ~ 7

Author(s):

Xianqiao Zeng ◽

Wei Mai ◽

Bo Shu ◽

Lina Yi ◽

Jing Lu ◽

...

Keyword(s):

Influenza A ◽

Guangdong Province ◽

H7n9 Infection

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Increased Interleukin-6 Levels in Nasal Lavage Samples following Experimental Influenza A Virus Infection

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.5.5.604-608.1998 ◽

1998 ◽

Vol 5 (5) ◽

pp. 604-608 ◽

Cited By ~ 57

Author(s):

Deborah Gentile ◽

William Doyle ◽

Theresa Whiteside ◽

Philip Fireman ◽

Frederick G. Hayden ◽

...

Keyword(s):

Virus Infection ◽

Influenza A Virus ◽

Interleukin 6 ◽

Influenza A ◽

Respiratory Infections ◽

Nasal Lavage ◽

Enzyme Linked Immunosorbent Assay ◽

Influenza A Virus Infection ◽

Systemic Symptoms ◽

Experimental Influenza

ABSTRACT Interleukin-6 (IL-6) is a pleotropic cytokine implicated in the pathogenesis of local inflammation during viral upper respiratory infections. This study determined if experimental influenza A virus infection causes local IL-6 production. Seventeen healthy, adult subjects were intranasally inoculated, by course drops, with a safety-tested strain of influenza A/Kawasaki/86 (H1N1) virus. Nasal lavage samples were collected, symptoms were recorded, and expelled nasal secretions were weighed once before and then daily for 8 days after the virus inoculation. Lavage samples were submitted for virus culture and were examined for IL-6 and IL-4 by enzyme-linked immunosorbent assay. The IL-6, but not IL-4, levels were significantly increased in the nasal lavage samples of the 12 subjects who shed virus but not in those of the 5 subjects who did not shed virus. Moreover, the elevations in IL-6 levels were related temporally to the development of nasal symptoms and secretions but not to systemic symptoms. These results suggest a role for locally produced IL-6 in the pathogenesis and expressed symptomatology of influenza A virus infection.

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Live Poultry Market Closure and Avian Influenza A (H7N9) infection in cities of China, 2013-2017: An ecological study

10.21203/rs.3.rs-16302/v1 ◽

2020 ◽

Author(s):

Ying Chen ◽

Jian Cheng ◽

Zhiwei Xu ◽

Wenbiao Hu ◽

Jiahai Lu

Keyword(s):

Avian Influenza ◽

Risk Reduction ◽

Influenza A ◽

Reduction Rate ◽

Dominant Factor ◽

Effective Measure ◽

Partial Closure ◽

Live Poultry ◽

H7n9 Infection ◽

The Impact

Abstract Background Previous studies have proven that the closure of live poultry markets (LPMs) was an effective intervention to reduce human risk of avian influenza A (H7N9) infection, but evidence is limited on the impact of scale and duration of LPMs closure on the transmission of H7N9. Method Five cities (i.e., Shanghai, Suzhou, Shenzhen, Guangzhou and Hangzhou) with the largest number of H7N9 cases in mainland China from 2013-2017 were selected in this study. Data on laboratory-confirmed H7N9 human cases in those five cities were obtained from the Chinese National Influenza Centre. The detailed information of LPMs closure (i.e., area and duration) was obtained from the Ministry of Agriculture. We used a generalized linear model with a Poisson link to estimate the effect of LPMs closure, reported as relative risk reduction (RRR). We used classification and regression trees (CARTs) to select and quantify the dominant factor of H7N9 infection. Results All five cities implemented the LPMs closure, and the risk of H7N9 infection decreased significantly after LPMs closure with RRR ranging from 0.80-0.93. Respectively, a long-term LPMs closure for 10-13 weeks elicited a sustained and highly significant risk reduction of H7N9 infection (RRR = 0.98). Short-time LPMs closure with 2 weeks in every epidemic did not reduce the risk of H7N9 infection (p>0.05). Partially closed LPMs in some suburbs contributed only 35% for reduction rate (RRR=0.35). Shenzhen implemented partial closure for first 3 epidemics (p>0.05) and all closure in the latest 2 epidemic waves (RRR=0.64). Conclusion Our findings suggest that LPMs all closure in whole city can be a highly effective measure comparing with partial closure (i.e. only urban closure, suburb and country remain open). Extend the duration of closure and consider permanently closing the LPMs will help improve the control effect. The effect of LPMs closure is greater than that of meteorology on H7N9 transmission.

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Live Poultry Market Closure and Avian Influenza A (H7N9) infection in cities of China, 2013-2017: An ecological study

10.21203/rs.3.rs-16302/v2 ◽

2020 ◽

Author(s):

Ying Chen ◽

Jian Cheng ◽

Zhiwei Xu ◽

Wenbiao Hu ◽

Jiahai Lu

Keyword(s):

Avian Influenza ◽

Risk Reduction ◽

Influenza A ◽

Reduction Rate ◽

Dominant Factor ◽

Effective Measure ◽

Partial Closure ◽

Live Poultry ◽

H7n9 Infection ◽

The Impact

Abstract Background Previous studies have proven that the closure of live poultry markets (LPMs) was an effective intervention to reduce human risk of avian influenza A (H7N9) infection, but evidence is limited on the impact of scale and duration of LPMs closure on the transmission of H7N9. Method Five cities (i.e., Shanghai, Suzhou, Shenzhen, Guangzhou and Hangzhou) with the largest number of H7N9 cases in mainland China from 2013-2017 were selected in this study. Data on laboratory-confirmed H7N9 human cases in those five cities were obtained from the Chinese National Influenza Centre. The detailed information of LPMs closure (i.e., area and duration) was obtained from the Ministry of Agriculture. We used a generalized linear model with a Poisson link to estimate the effect of LPMs closure, reported as relative risk reduction (RRR). We used classification and regression trees (CARTs) to select and quantify the dominant factor of H7N9 infection. Results All five cities implemented the LPMs closure, and the risk of H7N9 infection decreased significantly after LPMs closure with RRR ranging from 0.80-0.93. Respectively, a long-term LPMs closure for 10-13 weeks elicited a sustained and highly significant risk reduction of H7N9 infection (RRR = 0.98). Short-time LPMs closure with 2 weeks in every epidemic did not reduce the risk of H7N9 infection (p>0.05). Partially closed LPMs in some suburbs contributed only 35% for reduction rate (RRR=0.35). Shenzhen implemented partial closure for first 3 epidemics (p>0.05) and all closure in the latest 2 epidemic waves (RRR=0.64). Conclusion Our findings suggest that LPMs all closure in whole city can be a highly effective measure comparing with partial closure (i.e. only urban closure, suburb and country remain open). Extend the duration of closure and consider permanently closing the LPMs will help improve the control effect. The effect of LPMs closure is greater than that of meteorology on H7N9 transmission.

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A therapeutic study of an adamantane spiro compound in experimental influenza A infection in man

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/1.suppl_4.87 ◽

1975 ◽

Vol 1 (suppl 4) ◽

pp. 87-93 ◽

Cited By ~ 5

Author(s):

M. Arroyo ◽

A. S. Beare ◽

S. E. Reed ◽

J. W. Craig

Keyword(s):

Influenza A ◽

Spiro Compound ◽

Therapeutic Study ◽

Experimental Influenza

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Prolonged Evolution of Virus-Specific Memory T Cell Immunity after Severe Avian Influenza A (H7N9) Virus Infection

Journal of Virology ◽

10.1128/jvi.01024-18 ◽

2018 ◽

Vol 92 (17) ◽

Cited By ~ 12

Author(s):

Min Zhao ◽

Junbo Chen ◽

Shuguang Tan ◽

Tao Dong ◽

Hui Jiang ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Avian Influenza ◽

Influenza A ◽

T Cell Immunity ◽

H7n9 Virus ◽

Specific Memory ◽

Cell Immunity ◽

H7n9 Infection ◽

Over Time

ABSTRACT Since 2013, influenza A H7N9 virus has emerged as the most common avian influenza virus subtype causing human infection, and it is associated with a high fatality risk. However, the characteristics of immune memory in patients who have recovered from H7N9 infection are not well understood. We assembled a cohort of 45 H7N9 survivors followed for up to 15 months after infection. Humoral and cellular immune responses were analyzed in sequential samples obtained at 1.5 to 4 months, 6 to 8 months, and 12 to 15 months postinfection. H7N9-specific antibody concentrations declined over time, and protective antibodies persisted longer in severely ill patients admitted to the intensive care unit (ICU) and patients presenting with acute respiratory distress syndrome (ARDS) than in patients with mild disease. Frequencies of virus-specific gamma interferon (IFN-γ)-secreting T cells were lower in critically ill patients requiring ventilation than in patients without ventilation within 4 months after infection. The percentages of H7N9-specific IFN-γ-secreting T cells tended to increase over time in patients ≥60 years or in critically ill patients requiring ventilation. Elevated levels of antigen-specific CD8+ T cells expressing the lung-homing marker CD49a were observed at 6 to 8 months after H7N9 infection compared to those in samples obtained at 1.5 to 4 months. Our findings indicate the prolonged reconstruction and evolution of virus-specific T cell immunity in older or critically ill patients and have implications for T cell-directed immunization strategies. IMPORTANCE Avian influenza A H7N9 virus remains a major threat to public health. However, no previous studies have determined the characteristics and dynamics of virus-specific T cell immune memory in patients who have recovered from H7N9 infection. Our findings showed that establishment of H7N9-specific T cell memory after H7N9 infection was prolonged in older and severely affected patients. Severely ill patients mounted lower T cell responses in the first 4 months after infection, while T cell responses tended to increase over time in older and severely ill patients. Higher levels of antigen-specific CD8+ T cells expressing the lung-homing marker CD49a were detected at 6 to 8 months after infection. Our results indicated a long-term impact of H7N9 infection on virus-specific memory T cells. These findings advance our understanding of the dynamics of virus-specific memory T cell immunity after H7N9 infection, which is relevant to the development of T cell-based universal influenza vaccines.

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Lessons from Bacillus Calmette-Guérin: Harnessing Trained Immunity for Vaccine Development

Cells ◽

10.3390/cells9092109 ◽

2020 ◽

Vol 9 (9) ◽

pp. 2109

Author(s):

Samuel T. Pasco ◽

Juan Anguita

Keyword(s):

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Vaccine Development ◽

Vaccine Design ◽

Innate Immune ◽

Bacillus Calmette Guerin ◽

Adaptive Immune Responses ◽

Trained Immunity ◽

Adaptive Immune ◽

Potential Methods

Vaccine design traditionally focuses on inducing adaptive immune responses against a sole target pathogen. Considering that many microbes evade innate immune mechanisms to initiate infection, and in light of the discovery of epigenetically mediated innate immune training, the paradigm of vaccine design has the potential to change. The Bacillus Calmette-Guérin (BCG) vaccine induces some level of protection against Mycobacterium tuberculosis (Mtb) while stimulating trained immunity that correlates with lower mortality and increased protection against unrelated pathogens. This review will explore BCG-induced trained immunity, including the required pathways to establish this phenotype. Additionally, potential methods to improve or expand BCG trained immunity effects through alternative vaccine delivery and formulation methods will be discussed. Finally, advances in new anti-Mtb vaccines, other antimicrobial uses for BCG, and “innate memory-based vaccines” will be examined.

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