scholarly journals A Single Mutation at PB1 Residue 319 Dramatically Increases the Safety of PR8 Live Attenuated Influenza Vaccine in a Murine Model without Compromising Vaccine Efficacy

2015 ◽  
Vol 90 (5) ◽  
pp. 2702-2705 ◽  
Author(s):  
Andrew Cox ◽  
Stephen Dewhurst
Keyword(s):  
At Risk ◽  
Amino Acid ◽  
Influenza Vaccine ◽  
Murine Model ◽  
Vaccine Efficacy ◽  
Protective Efficacy ◽  
Fold Increase ◽  
Single Mutation ◽  
Live Attenuated Influenza Vaccine ◽  
Amino Acid Mutations

The live attenuated influenza vaccine (LAIV) is preferentially recommended for use in most children yet remains unsafe for the groups most at risk. Here we have improved the safety of a mouse-adapted live attenuated influenza vaccine containing the same attenuating amino acid mutations as in human LAIV by adding an additional mutation at PB1 residue 319. This results in a vaccine with a 20-fold decrease in protective efficacy and a 10,000-fold increase in safety.

scholarly journals HA and M2 sequences alter the replication of 2013-16 H1 Live Attenuated Influenza Vaccine Infection in Human Nasal Epithelial Cell cultures

2021 ◽  
Author(s):  
Jessica D Resnick ◽  
Laura M Canaday ◽  
Hsuan Liu ◽  
Harrison Powell ◽  
Alyssa M McCoy ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Cell Cultures ◽  
Vaccine Efficacy ◽  
Infectious Virus ◽  
Mdck Cells ◽  
Virus Production ◽  
Rna Packaging ◽  
Nasal Epithelial Cell ◽  
Positive Effects ◽  
Live Attenuated Influenza Vaccine

From 2013-2016, the H1N1 component of live, attenuated influenza vaccine (LAIV) performed very poorly in contrast to the inactivated influenza vaccine. We utilized a primary, differentiated human nasal epithelial (hNEC) culture system to assess the replication differences between isogenic LAIVs containing the HA segment from either A/Bolivia/559/2013 (rBol), which showed poor vaccine efficacy, and A/Slovenia/2903/2015 (rSlov), which had restored reasonable vaccine efficacy. While there were minimal differences in infectious virus production in Madin-Darby Canine Kidney (MDCK) cells, the rSlov LAIV showed markedly improved replication in hNEC cultures at both 32oC and 37oC, demonstrating that the HA segment alone could impact LAIV replication. The rSlov-infected hNEC cultures showed stronger production of interferon and proinflammatory chemokines which might also be contributing to the increased overall vaccine effectiveness of the rSlov LAIV through enhanced recruitment and activation of immune cells. The introduction of an M2-S86A mutation had no positive effects on H1 LAIV replication in hNEC cultures, in contrast to the increased infectious virus production seen with that mutation in an H3 LAIV. No obvious defects in viral RNA packaging were detected, suggesting the HA function may be driving the differential infectious virus production in hNEC cultures. The use of physiologically relevant temperatures and primary cell cultures demonstrated that candidate LAIVs can replicate efficiently, which is a necessary property for effective vaccines.

scholarly journals Increasing the Safety Profile of the Master Donor Live Attenuated Influenza Vaccine

Pathogens ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 86 ◽  
Author(s):  
Thomas A. Hilimire ◽  
Aitor Nogales ◽  
Kevin Chiem ◽  
Javier Ortego ◽  
Luis Martinez-Sobrido
Keyword(s):  
Influenza Vaccine ◽  
Influenza A ◽  
Protective Efficacy ◽  
Influenza Infection ◽  
Vaccination Campaign ◽  
The Elderly ◽  
Antiviral Responses ◽  
Live Attenuated Influenza Vaccine ◽  
Ann Arbor ◽  
Health Burdens

Seasonal influenza epidemics remain one of the largest public health burdens nowadays. The best and most effective strategy to date in preventing influenza infection is a worldwide vaccination campaign. Currently, two vaccines are available to the public for the treatment of influenza infection, the chemically Inactivated Influenza Vaccine (IIV) and the Live Attenuated Influenza Vaccine (LAIV). However, the LAIV is not recommended for parts of the population, such as children under the age of two, immunocompromised individuals, the elderly, and pregnant adults. In order to improve the safety of the LAIV and make it available to more of the population, we sought to further attenuate the LAIV. In this study, we demonstrate that the influenza A virus (IAV) master donor virus (MDV) A/Ann Arbor/6/60 H2N2 LAIV can inhibit host gene expression using both the PA-X and NS1 proteins. Furthermore, we show that by removing PA-X, we can limit the replication of the MDV LAIV in a mouse model, while maintaining full protective efficacy. This work demonstrates a broadly applicable strategy of tuning the amount of host antiviral responses induced by the IAV MDV for the development of newer and safer LAIVs. Moreover, our results also demonstrate, for the first time, the feasibility of genetically manipulating the backbone of the IAV MDV to improve the efficacy of the current IAV LAIV.

scholarly journals Identification and Analysis of Amino Acid Mutations in Porin IB That Mediate Intermediate-Level Resistance to Penicillin and Tetracycline in Neisseria gonorrhoeae

2002 ◽  
Vol 46 (9) ◽  
pp. 2811-2820 ◽  
Author(s):  
Melanie Olesky ◽  
Marcia Hobbs ◽  
Robert A. Nicholas
Keyword(s):  
Amino Acids ◽  
Antibiotic Resistance ◽  
Amino Acid ◽  
Neisseria Gonorrhoeae ◽  
Tetracycline Resistance ◽  
Recipient Strain ◽  
Site Directed Mutagenesis ◽  
Single Mutation ◽  
Resistance To Penicillin ◽  
Amino Acid Mutations

ABSTRACT PenB is the third resistance determinant in the stepwise acquisition of multiple resistance genes in chromosomally mediated resistant Neisseria gonorrhoeae (CMRNG). Alterations in porIB , one of two alleles at the por locus that encodes the outer membrane protein porin IB (PIB), were recently reported to be responsible for the increased resistance to penicillin and tetracycline conferred by penB, but the specific mutations conferring antibiotic resistance were not identified experimentally. To determine which amino acids in PIB confer increased resistance, we transformed a recipient strain with chimeras of the porIB genes from strains FA1090 and FA140 (penB2). These studies revealed that two amino acid changes, G120D and A121D, were both necessary and sufficient to confer increased resistance to penicillin and tetracycline. Site-saturation and site-directed mutagenesis of Gly-120 and Ala-121 revealed that both a single mutation, G120K, and the double mutations G120R A121H and G120P A121P also conferred antibiotic resistance to the recipient strain. The identical mutations in PIA increased penicillin and tetracycline resistance either moderately or not at all. Analysis of porIB genes present in the GenBank database from 51 clinical isolates demonstrated that lysine and aspartate mutations at positions 120 and/or 121 also occur in nature. These studies demonstrate that charged amino acids at positions 120 and 121 in PIB are highly preferential for conferring resistance to penicillin and tetracycline in N. gonorrhoeae.

scholarly journals HAI and NAI titer correlates of inactivated and live attenuated influenza vaccine efficacy

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Peter B Gilbert ◽  
Youyi Fong ◽  
Michal Juraska ◽  
Lindsay N Carpp ◽  
Arnold S Monto ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Vaccine Efficacy ◽  
Live Attenuated Influenza Vaccine

scholarly journals Protective efficacy of inactivated reverse genetics based equine influenza vaccine candidate adjuvanted with MontanideTM Pet Gel in murine model

2019 ◽  
Vol 81 (12) ◽  
pp. 1753-1762 ◽  
Author(s):  
Manu Kurian MATHEW ◽  
Nitin VIRMANI ◽  
Bidhan Chandra BERA ◽  
Taruna ANAND ◽  
Ramesh KUMAR ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Murine Model ◽  
Reverse Genetics ◽  
Vaccine Candidate ◽  
Protective Efficacy ◽  
Equine Influenza

scholarly journals The prediction of Influenza A/H3N2 Vaccine Efficacy using samples obtained from Indonesian Hajj pilgrims in 2013

2018 ◽  
Vol 9 (1) ◽  
pp. 1-7
Author(s):  
Agustiningsih Agustiningsih ◽  
Kartika Dewi Puspa ◽  
Hartanti Dian Ikawati ◽  
Eka Pratiwi ◽  
Ririn Ramadhany ◽  
...  
Keyword(s):  
Amino Acid ◽  
Influenza Vaccine ◽  
Vaccine Strain ◽  
Vaccine Efficacy ◽  
Influenza A ◽  
Influenza Viruses ◽  
Health Science ◽  
H3n2 Virus ◽  
Science Journal ◽  
Virus Influenza

Abstrak Latar Belakang: Vaksinasi merupakan salah satu cara efektif dalam mengontrol dan mengurangi beban penyakit yang disebabkan oleh Influenza. Akan tetapi, efikasi vaksin bisa bervariasi jika strain yang digunakan untuk vaksin berbeda dengan strain yang bersirkulasi di dunia. Hal ini menunjukan pentingnya melakukan analisa prediksi efikasi vaksin. Pada studi ini, prediksi efikasi vaksin Influenza A/H3N2 dilakukan berdasarkan perhitungan antigenic distance strain vaksin WHO dengan virus influenza yang berasal dari jemaah Haj iIndonesia pada tahun 2013. Metode: Sekuensing gen HA dilakukan terhadap dua sampel tersimpan yang terkonfirmasi positif Influenza A/ H3N2 yang berasal dari jemaah Haji Indonesia tahun 2013. Pepitope Calculator digunakan untuk menghitung antigenic distance dari dua strain virus influenza dan dilanjutkan dengan perhitungan Pepitope value. Vaksin strain yang direkomendasikan oleh WHO; A/Texas/50/2012, A/Switzerland/9715293/2013, A/HongKong/4801/2014 dan dua virus yang diambil dari jemaah Haji Indonesia pada tahun 2013 dianalisa pada studi ini. Hasil: Prediksi efikasi vaksin yang direkomendasikan WHO tahun 2013 (A/Texas/50/2012) dengan sampel yang berasal dari jemaah Haji Indonesia tahun 2013 menunjukkan hasil lebih rendah dibandingkan dengan strain vaksin untuk musim flu pada tahun selanjutnya. Hasil ini sesuai dengan hasil analisis filogenetik dan perbandingan asam amino dimana sampel pada studi ini berkerabat lebih dekat dengan strain vaksin untuk musim flu selanjutnya dengan perbedaan asam amino yang lebih sedikit di bagian epitope protein HA dibandingkan dengan vaksin tahun 2013. Kesimpulan: Perhitungan efikasi vaksin menggunakan antigenic distance antara strain vaksin WHO dan virus yang menginfeksi jemaah haji Indonesia pada tahun 2013 menunjukkan hasil yang rendah. (Health Science Journal of Indonesia 2018;9(1):1-7) Keywords: Efikasi vaksin, Influenza A/H3N2, jemaah Haji, Indonesia Abstract Background: Influenza vaccination is an effective approach to control and reduce the disease burden of influenza viruses. However, the efficacy of influenza vaccine varies every year due to the different antigenic distance between vaccine and the circulating influenza strains globally and therefore necessitates the study of vaccine efficacy (VE). This study describes the prediction of Influenza A/H3N2 VE based on antigenic distances WHO vaccine strains and the virus obtained from Indonesian Hajj pilgrims in 2013. Methods: Coding between Sequence of HA gene of Influenza A/H3N2 virus was obtained from archival samples of Indonesian Hajj Pilgrims in 2013. Pepitope value calculation using Pepitope Calculator to measure the antigenic distance of HA sequences of two influenza strains was implemented. The HA sequences of WHO vaccine strains: A/ Texas/50/2012, A/Switzerland/9715293/2013, A/HongKong/4801/2014 and two influenza viruses from Indonesian Hajj pilgrims in 2013 were analyzed. Results: This study predicted that influenza vaccine strain recommended by WHO for 2013 (A/Texas/50/2012) have low efficacy to the influenza virus obtained from Indonesian Hajj Pilgrim in 2013 while showing higher efficacy to vaccine strain recommended for the following year. This result was in line with phylogenetic analysis and amino acid differences in which the samples in this study were grouped together with vaccine strain in following years and had less amino acid differences in epitope located in HA protein compared with 2013 vaccine strain. Conclusion: The prediction of VE using the antigenic distance measurement between WHO vaccine strain and Indonesian Hajj pilgrim collected in 2013, is considered low. (Health Science Journal of Indonesia 2018;9(1):1-7) Keywords: Vaccine efficacy, influenza A/H3N2 virus, Hajj pilgrim, Indonesia

scholarly journals Predicting influenza H3N2 vaccine efficacy from evolution of the dominant epitope

2018 ◽  
Author(s):  
Melia E. Bonomo ◽  
Michael W. Deem
Keyword(s):  
Amino Acid ◽  
Influenza Vaccine ◽  
Vaccine Efficacy ◽  
Influenza A ◽  
Candidate Vaccine ◽  
Amino Acid Substitutions ◽  
H3n2 Vaccine ◽  
Disease Attack ◽  
Dominant Epitope ◽  
Influenza H3n2

AbstractWe predict vaccine efficacy with a measure of antigenic distance between influenza A(H3N2) and candidate vaccine viruses based on amino acid substitutions in the dominant epitopes. In 2016-2017, our model predicts 19% efficacy compared to 20% observed. This tool assists candidate vaccine selection by predicting human protection against circulating strains.40-word summary of main pointOur pepitope model predicts the ability of the influenza vaccine to reduce the A(H3N2) disease attack rate, with an r^2=0.77. This fast, sequence-based method compliments strain-to-strain antigenic comparisons from ferret models and provides antigenic comparisons for all circulating sequences.

scholarly journals Impact of Pre-Existing Immunity on Live Attenuated Influenza Vaccine-Induced Cross-Protective Immunity

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 459 ◽  
Author(s):  
Sreeja Roy ◽  
Clare M Williams ◽  
Julian Pardo ◽  
Danushka K Wijesundara ◽  
Yoichi Furuya
Keyword(s):  
T Cell ◽  
Influenza Vaccine ◽  
Cellular Immunity ◽  
Specific Antibody ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Cross Protection ◽  
Antibody Responses ◽  
Live Attenuated Influenza Vaccine ◽  
Heterologous Challenge

The efficacy of the intranasally (i.n.) delivered live attenuated influenza vaccine (LAIV) is variable and, in some seasons, suboptimal. In this study, we report that LAIV exhibits cross-protective efficacy in mice, potentially associated with cellular immunity as opposed to antigen-specific antibody responses. However, pre-exposure to the intramuscularly (i.m.) delivered inactivated influenza vaccine (IIV) severely impaired LAIV-induced cross-protection against heterologous challenge, potentially by inhibiting replication of LAIV. Our findings suggest that pre-existing immunity afforded by IIV suppresses cross-protective T cell immunogenicity of LAIV.

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