Live Attenuated Influenza Vaccine as a Nasal Model for Influenza Infection

2019 ◽  
Author(s):  
Keyword(s):  
Influenza Vaccine ◽  
Influenza Infection ◽  
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.

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.

Nontraditional Uses of Live Attenuated Influenza Vaccine: School-Located Influenza Vaccination

2020 ◽  
Vol 9 (Supplement_1) ◽  
pp. S19-S23 ◽  
Author(s):  
Geoffrey A Weinberg
Keyword(s):  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
Influenza Infection ◽  
Evidence Base ◽  
Vaccine Effectiveness ◽  
Vaccination Rates ◽  
Live Attenuated Influenza Vaccine

Abstract Immunization against influenza continues to be the best method of preventing influenza infection in children, and additionally, indirectly helping to lower disease in adults, given the role of children as “spreaders” of influenza to the community at large. An increasing evidence base exists for the use of school-located influenza vaccination (SLIV) programs to increase the influenza vaccination rates among children. Live, attenuated influenza vaccine (LAIV) has unique characteristics that make it useful for SLIV programs, including ease of immunization without needles, faster delivery, and in many (but not all) years, good vaccine effectiveness. Reviewed herein are results of selected published trials as well as guidance on planning a successful SLIV program.

scholarly journals Severity of heterosubtypic influenza virus infection in ferrets is reduced by live attenuated influenza vaccine

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Anthony C. Marriott ◽  
Karen E. Gooch ◽  
Phillip J. Brown ◽  
Kathryn A. Ryan ◽  
Nicola J. Jones ◽  
...  
Keyword(s):  
Influenza Vaccine ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Influenza Infection ◽  
Influenza Virus Infection ◽  
H3n2 Virus ◽  
Live Attenuated Influenza Vaccine ◽  
Inactivated Vaccines ◽  
Ifn Γ ◽  
Cellular Immune

AbstractLive attenuated influenza vaccine (LAIV) is widely used to protect humans from seasonal influenza infection, particularly in children. In contrast to inactivated vaccines, the LAIV can induce both mucosal and cellular immune responses. Here we show that a single dose of monovalent H1N1pdm09-specific LAIV in the ferret model is fully protective against a subsequent wild-type H1N1pdm09 challenge, and furthermore reduces the severity of disease following challenge with a different influenza A subtype (H3N2). The reduced severity comprised reductions in weight loss and fever, as well as more rapid clearance of virus, compared to non-vaccinated H3N2-challenged ferrets. No H3N2-neutralizing antibodies were detected in vaccinated ferret sera. Rather, heterosubtypic protection correlated with interferon-gamma+ (IFN-γ+) T-cell responses measured in peripheral blood and in lung lymphocytes. The IFN-γ+ cells were cross-reactive to H3N2 virus even when obtained from vaccinated animals that had never been exposed to H3N2 virus. We believe this study provides compelling evidence that the LAIV can provide a significant reduction in infection and symptoms when challenged with heterosubtypic influenza strains not included in the LAIV, highlighting the importance of cross-reactive T-cells in the design of a universal influenza vaccine.

scholarly journals Influenza vaccine failure in the tropics: a retrospective cohort study of waning effectiveness

2020 ◽  
Vol 148 ◽  
Author(s):  
B. E. Young ◽  
T. M. Mak ◽  
L. W. Ang ◽  
S. Sadarangani ◽  
H. J. Ho ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Cohort Study ◽  
Influenza Vaccine ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Influenza Infection ◽  
Winter Season ◽  
Temperate Climate ◽  
Vaccine Failure ◽  
Virus Activity

Abstract Influenza vaccine effectiveness (VE) wanes over the course of a temperate climate winter season but little data are available from tropical countries with year-round influenza virus activity. In Singapore, a retrospective cohort study of adults vaccinated from 2013 to 2017 was conducted. Influenza vaccine failure was defined as hospital admission with polymerase chain reaction-confirmed influenza infection 2–49 weeks after vaccination. Relative VE was calculated by splitting the follow-up period into 8-week episodes (Lexis expansion) and the odds of influenza infection in the first 8-week period after vaccination (weeks 2–9) compared with subsequent 8-week periods using multivariable logistic regression adjusting for patient factors and influenza virus activity. Records of 19 298 influenza vaccinations were analysed with 617 (3.2%) influenza infections. Relative VE was stable for the first 26 weeks post-vaccination, but then declined for all three influenza types/subtypes to 69% at weeks 42–49 (95% confidence interval (CI) 52–92%, P = 0.011). VE declined fastest in older adults, in individuals with chronic pulmonary disease and in those who had been previously vaccinated within the last 2 years. Vaccine failure was significantly associated with a change in recommended vaccine strains between vaccination and observation period (adjusted odds ratio 1.26, 95% CI 1.06–1.50, P = 0.010).

Efficacy of seasonal live attenuated influenza vaccine against virus replication and transmission of a pandemic 2009 H1N1 virus in ferrets

Vaccine ◽  
2011 ◽  
Vol 29 (16) ◽  
pp. 2887-2894 ◽  
Author(s):  
Melissa B. Pearce ◽  
Jessica A. Belser ◽  
Katherine V. Houser ◽  
Jacqueline M. Katz ◽  
Terrence M. Tumpey
Keyword(s):  
Influenza Vaccine ◽  
Virus Replication ◽  
H1n1 Virus ◽  
Live Attenuated Influenza Vaccine ◽  
2009 H1n1
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