1.Mucosal Immunization with Recombinant Adenovirus Encoding Soluble Globular Head of Hemagglutinin Protects Mice Against Lethal Influenza Virus Infection.
Joo Young KIM ; Youngjoo CHOI ; Huan H NGUYEN ; Man Ki SONG ; Jun CHANG
Immune Network 2013;13(6):275-282
Influenza virus is one of the major sources of respiratory tract infection. Due to antigenic drift in surface glycoproteins the virus causes annual epidemics with severe morbidity and mortality. Although hemagglutinin (HA) is one of the highly variable surface glycoproteins of the influenza virus, it remains the most attractive target for vaccine development against seasonal influenza infection because antibodies generated against HA provide virus neutralization and subsequent protection against the virus infection. Combination of recombinant adenovirus (rAd) vector-based vaccine and mucosal administration is a promising regimen for safe and effective vaccination against influenza. In this study, we constructed rAd encoding the globular head region of HA from A/Puerto Rico/8/34 virus as vaccine candidate. The rAd vaccine was engineered to express high level of the protein in secreted form. Intranasal or sublingual immunization of mice with the rAd-based vaccine candidates induced significant levels of sustained HA-specific mucosal IgA and IgG. When challenged with lethal dose of homologous virus, the vaccinated mice were completely protected from the infection. The results demonstrate that intranasal or sublingual vaccination with HA-encoding rAd elicits protective immunity against infection with homologous influenza virus. This finding underlines the potential of our recombinant adenovirus-based influenza vaccine candidate for both efficacy and rapid production.
Adenoviridae*
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Administration, Mucosal
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Animals
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Antibodies
;
Head*
;
Hemagglutinins*
;
Immunization*
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Immunoglobulin A
;
Immunoglobulin G
;
Influenza Vaccines
;
Influenza, Human*
;
Membrane Glycoproteins
;
Mice*
;
Mortality
;
Orthomyxoviridae*
;
Respiratory Tract Infections
;
Seasons
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Vaccination
;
Viruses
2.Impact of fatty liver on long-term outcomes in chronic hepatitis B: a systematic review and matched analysis of individual patient data meta-analysis
Yu Jun WONG ; Vy H. NGUYEN ; Hwai-I YANG ; Jie LI ; Michael Huan LE ; Wan-Jung WU ; Nicole Xinrong HAN ; Khi Yung FONG ; Elizebeth CHEN ; Connie WONG ; Fajuan RUI ; Xiaoming XU ; Qi XUE ; Xin Yu HU ; Wei Qiang LEOW ; George Boon-Bee GOH ; Ramsey CHEUNG ; Grace WONG ; Vincent Wai-Sun WONG ; Ming-Whei YU ; Mindie H. NGUYEN
Clinical and Molecular Hepatology 2023;29(3):705-720
Background/Aims:
Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients.
Methods:
We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment.
Results:
We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001).
Conclusions
IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.