scholarly journals Pan-Influenza A Protection by Prime–Boost Vaccination with Cold-Adapted Live-Attenuated Influenza Vaccine in a Mouse Model

2018 ◽  
Vol 9 ◽  
Author(s):  
Yo Han Jang ◽  
Joo Young Kim ◽  
Young Ho Byun ◽  
Ahyun Son ◽  
Jeong-Yoon Lee ◽  
...  
Keyword(s):  
Mouse Model ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Cold Adapted ◽  
Boost Vaccination ◽  
Live Attenuated Influenza Vaccine

scholarly journals Effectiveness of seasonal influenza vaccine for adults and children in preventing laboratory-confirmed influenza in primary care in the United Kingdom: 2015/16 end-of-season results

2016 ◽  
Vol 21 (38) ◽  
Author(s):  
Richard Pebody ◽  
Fiona Warburton ◽  
Joanna Ellis ◽  
Nick Andrews ◽  
Alison Potts ◽  
...  
Keyword(s):  
Primary Care ◽  
United Kingdom ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Immunisation Programme ◽  
Influenza B ◽  
Live Attenuated Influenza Vaccine ◽  
The United Kingdom ◽  
Influenza A H1n1 ◽  
The Uk

The United Kingdom (UK) is in the third season of introducing universal paediatric influenza vaccination with a quadrivalent live attenuated influenza vaccine (LAIV). The 2015/16 season in the UK was initially dominated by influenza A(H1N1)pdm09 and then influenza of B/Victoria lineage, not contained in that season’s adult trivalent inactivated influenza vaccine (IIV). Overall adjusted end-of-season vaccine effectiveness (VE) was 52.4% (95% confidence interval (CI): 41.0–61.6) against influenza-confirmed primary care consultation, 54.5% (95% CI: 41.6–64.5) against influenza A(H1N1)pdm09 and 54.2% (95% CI: 33.1–68.6) against influenza B. In 2–17 year-olds, adjusted VE for LAIV was 57.6% (95% CI: 25.1 to 76.0) against any influenza, 81.4% (95% CI: 39.6–94.3) against influenza B and 41.5% (95% CI: −8.5 to 68.5) against influenza A(H1N1)pdm09. These estimates demonstrate moderate to good levels of protection, particularly against influenza B in children, but relatively less against influenza A(H1N1)pdm09. Despite lineage mismatch in the trivalent IIV, adults younger than 65 years were still protected against influenza B. These results provide reassurance for the UK to continue its influenza immunisation programme planned for 2016/17.

scholarly journals Master donor viruses A/Leningrad/134/17/57 (H2N2) and B/USSR/60/69 and derived reassortants used in live attenuated influenza vaccine (LAIV) do not display neurovirulent properties in a mouse model

2010 ◽  
Vol 155 (9) ◽  
pp. 1391-1399 ◽  
Author(s):  
J. Theo M. Voeten ◽  
Irina V. Kiseleva ◽  
Harrie L. Glansbeek ◽  
Stephanie M. C. Basten ◽  
Sandra K. M. Drieszen-van der Cruijsen ◽  
...  
Keyword(s):  
Mouse Model ◽  
Influenza Vaccine ◽  
Live Attenuated Influenza Vaccine

scholarly journals A Live Attenuated Influenza Vaccine Elicits Enhanced Heterologous Protection When the Internal Genes of the Vaccine Are Matched to Those of the Challenge Virus

2019 ◽  
Vol 94 (4) ◽  
Author(s):  
Andrew Smith ◽  
Laura Rodriguez ◽  
Maya El Ghouayel ◽  
Aitor Nogales ◽  
Jeffrey M. Chamberlain ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Influenza A ◽  
H1n1 Virus ◽  
Influenza Infection ◽  
Influenza Viruses ◽  
Influenza Vaccines ◽  
Temperature Sensitive ◽  
Live Attenuated Influenza Vaccine ◽  
Cell Immunity

ABSTRACT Influenza A virus (IAV) causes significant morbidity and mortality, despite the availability of viral vaccines. The efficacy of live attenuated influenza vaccines (LAIVs) has been especially poor in recent years. One potential reason is that the master donor virus (MDV), on which all LAIVs are based, contains either the internal genes of the 1960 A/Ann Arbor/6/60 or the 1957 A/Leningrad/17/57 H2N2 viruses (i.e., they diverge considerably from currently circulating strains). We previously showed that introduction of the temperature-sensitive (ts) residue signature of the AA/60 MDV into a 2009 pandemic A/California/04/09 H1N1 virus (Cal/09) results in only 10-fold in vivo attenuation in mice. We have previously shown that the ts residue signature of the Russian A/Leningrad/17/57 H2N2 LAIV (Len LAIV) more robustly attenuates the prototypical A/Puerto Rico/8/1934 (PR8) H1N1 virus. In this work, we therefore introduced the ts signature from Len LAIV into Cal/09. This new Cal/09 LAIV is ts in vitro, highly attenuated (att) in mice, and protects from a lethal homologous challenge. In addition, when our Cal/09 LAIV with PR8 hemagglutinin and neuraminidase was used to vaccinate mice, it provided enhanced protection against a wild-type Cal/09 challenge relative to a PR8 LAIV with the same attenuating mutations. These findings suggest it may be possible to improve the efficacy of LAIVs by better matching the sequence of the MDV to currently circulating strains. IMPORTANCE Seasonal influenza infection remains a major cause of disease and death, underscoring the need for improved vaccines. Among current influenza vaccines, the live attenuated influenza vaccine (LAIV) is unique in its ability to elicit T-cell immunity to the conserved internal proteins of the virus. Despite this, LAIV has shown limited efficacy in recent years. One possible reason is that the conserved, internal genes of all current LAIVs derive from virus strains that were isolated between 1957 and 1960 and that, as a result, do not resemble currently circulating influenza viruses. We have therefore developed and tested a new LAIV, based on a currently circulating pandemic strain of influenza. Our results show that this new LAIV elicits improved protective immunity compared to a more conventional LAIV.

Safety of cold-adapted live attenuated influenza vaccine in a large cohort of children and adolescents

2004 ◽  
Vol 23 (2) ◽  
pp. 138-144 ◽  
Author(s):  
RANDY BERGEN ◽  
STEVE BLACK ◽  
HENRY SHINEFIELD ◽  
EDWIN LEWIS ◽  
PAULA RAY ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Children And Adolescents ◽  
Large Cohort ◽  
Cold Adapted ◽  
Live Attenuated Influenza Vaccine

scholarly journals Safety, Immunogenicity, and Protective Efficacy of a Chimeric A/B Live Attenuated Influenza Vaccine in a Mouse Model

2021 ◽  
Vol 9 (2) ◽  
pp. 259
Author(s):  
Ekaterina Stepanova ◽  
Elena Krutikova ◽  
Pei-Fong Wong ◽  
Victoria Matyushenko ◽  
Ekaterina Bazhenova ◽  
...  
Keyword(s):  
T Cell ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Type A ◽  
Influenza Viruses ◽  
Effector Memory ◽  
Influenza B Virus ◽  
Influenza B ◽  
Live Attenuated Influenza Vaccine ◽  
B Virus

Influenza A and B viruses cause significant morbidity and mortality worldwide. Current influenza vaccines are composed of three or four strains: A/H1N1, A/H3N2, and B (Victoria and Yamagata lineages). It is of great interest if immunization against both type A and B influenza viruses can be combined in a single vaccine strain, thus reducing the cost of vaccine production and the possibility of strain interference within the multicomponent vaccine. In the current study, we developed an experimental live cold-adapted influenza intertype reassortant (influenza A and B) vaccine on the live attenuated influenza vaccine (LAIV) A/Leningrad/134/17/57 backbone. Hemagglutinin (HA) and neuraminidase (NA) functional domains were inherited from the influenza B/Brisbane/60/2008 strain, whereas their packaging signals were substituted with appropriate fragments of influenza A virus genes. The recombinant A/B virus efficiently replicated in eggs and Madin–Darby Canine Kidney (MDCK) cells under optimal conditions, temperature-sensitive phenotype was maintained, and its antigenic properties matched the influenza B parental virus. The chimeric vaccine was attenuated in mice: after intranasal immunization, viral replication was seen only in nasal turbinates but not in the lungs. Immunological studies demonstrated the induction of IgG antibody responses against the influenza A and B virus, whereas hemagglutination inhibition (HAI) and neutralizing antibodies were detected only against the influenza B virus, resulting in significant protection of immunized animals against influenza B virus challenge. IFNγ-secreting CD8 effector memory T cells (CD44+CD62L−) were detected in mouse splenocytes after stimulation with the specific influenza A peptide (NP366); however, the T-cell response was not sufficient to protect animals against infection with a high-dose mouse-adapted A/California/07/2009 (H1N1pdm09) virus, most probably due to the mismatch of key T-cell epitopes of the H1N1 virus and the LAIV backbone. Overall, generation of the chimeric A/B LAIV virus on a licensed LAIV backbone demonstrated prospects for the development of safe and efficacious vaccine candidates that afford combined protection against both type A and type B influenza viruses; however, further optimization of the T-cell epitope content within the LAIV backbone may be required.

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 Safety, efficacy and effectiveness of cold-adapted, live, attenuated, trivalent, intranasal influenza vaccine in adults and children

2001 ◽  
Vol 356 (1416) ◽  
pp. 1947-1951 ◽  
Author(s):  
Robert B. Belshe ◽  
William C. Gruber
Keyword(s):  
Influenza Vaccine ◽  
Influenza A ◽  
Febrile Illness ◽  
Respiratory Illness ◽  
Antibiotic Use ◽  
Double Blind ◽  
Cold Adapted ◽  
Adults And Children ◽  
The Impact ◽  
Significant Health

Studies in children and adults revealed cold–adapted, live, attenuated, trivalent, intranasal influenza vaccine (CAIV–T) to be well accepted, well tolerated and highly protective against culture–confirmed influenza, and to provide significant health benefits. A 2 year, multicentre, double–blind, placebo–controlled efficacy field trial of CAIV–T in children aged 15–71 months with annual re–immunization revealed the vaccine to be highly protective against culture–confirmed influenza. Vaccine induced serum and secretory antibodies in vaccinated children. Overall, during 2 years of study, vaccine was 92% protective against culture–confirmed influenza. During the second year of study the vaccine was 86% protective against influenza A/Sydney/5/97–like virus, a significantly drifted strain not well matched to the vaccine. Antibody studies on children given CAIV–T revealed that high titres of cross–reacting antibodies to influenza A/Sydney/5/97 were induced with vaccination by live attenuated influenza A/Wuhan/359/95–like vaccine. Effectiveness measures revealed significant reductions in febrile illness (21% reduction in year 1, 19% reduction in year 2), febrile otitis media (33% reduction in year 1, 16% reduction in year 2) and associated antibiotic use among vaccinated children compared with placebo recipients. In adults, vaccination with CAIV–T resulted in protection during experimental challenge with virulent wild–type viruses. An effectiveness trial in adults demonstrated significant benefits of CAIV–T vaccine (28% reduction in days of missed work for febrile upper respiratory illness days with associated 45% reduction in days taking antibiotics). General use of CAIV–T has the potential to significantly reduce the impact of influenza in children and adults.

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