tetano
Editor, Senior Moderator
J Virol. 2019 Nov 20. pii: JVI.01065-19. doi: 10.1128/JVI.01065-19. [Epub ahead of print] [h=1]A live-attenuated influenza vaccine (LAIV) elicits enhanced heterologous protection when the internal genes of the vaccine are matched to the challenge virus.[/h]
Smith A[SUP]1,[/SUP][SUP]2[/SUP], Rodriguez L[SUP]1[/SUP], Ghouayel ME[SUP]1[/SUP], Nogales A[SUP]1[/SUP], Chamberlain JM[SUP]1[/SUP], Sortino K[SUP]1[/SUP], Reilly E[SUP]1,[/SUP][SUP]3[/SUP], Feng C[SUP]4[/SUP], Topham DJ[SUP]1,[/SUP][SUP]3[/SUP], Mart?nez-Sobrido L[SUP]1[/SUP], Dewhurst S[SUP]5[/SUP].
[h=3]Author information[/h] 1 Department of Microbiology and Immunology, University of Rochester, Rochester, New York. 2 Medical Scientist Training Program (MSTP), University of Rochester, Rochester, New York. 3 David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York. 4 Department of Biostatistics and Computational Biology, 265 Crittenden Boulevard, CU 420630, University of Rochester, Rochester, New York. 5 Department of Microbiology and Immunology, University of Rochester, Rochester, New York Stephen_Dewhurst@urmc.rochester.edu.
[h=3]Abstract[/h] 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 HA and NA 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 when compared to a more conventional LAIV.
Copyright ? 2019 Smith et al.
PMID: 31748399 DOI: 10.1128/JVI.01065-19
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Smith A[SUP]1,[/SUP][SUP]2[/SUP], Rodriguez L[SUP]1[/SUP], Ghouayel ME[SUP]1[/SUP], Nogales A[SUP]1[/SUP], Chamberlain JM[SUP]1[/SUP], Sortino K[SUP]1[/SUP], Reilly E[SUP]1,[/SUP][SUP]3[/SUP], Feng C[SUP]4[/SUP], Topham DJ[SUP]1,[/SUP][SUP]3[/SUP], Mart?nez-Sobrido L[SUP]1[/SUP], Dewhurst S[SUP]5[/SUP].
[h=3]Author information[/h] 1 Department of Microbiology and Immunology, University of Rochester, Rochester, New York. 2 Medical Scientist Training Program (MSTP), University of Rochester, Rochester, New York. 3 David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, New York. 4 Department of Biostatistics and Computational Biology, 265 Crittenden Boulevard, CU 420630, University of Rochester, Rochester, New York. 5 Department of Microbiology and Immunology, University of Rochester, Rochester, New York Stephen_Dewhurst@urmc.rochester.edu.
[h=3]Abstract[/h] 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 HA and NA 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 when compared to a more conventional LAIV.
Copyright ? 2019 Smith et al.
PMID: 31748399 DOI: 10.1128/JVI.01065-19
Free full text