Evaluatingα-galactosylceramide as an adjuvant for live attenuated infuenza vaccines in pigs  

作　　者：Bianca L.Artiaga Igor Morozov Russell Ransburgh Taeyong Kwon Velmurugan Balaraman Sabarish V.Indran Darling Melany De Carvalho Madrid Weihong Gu Jamie Henningson Wenjun Ma Jürgen A.Richt John P.Driver 

机构地区：[1]Department of Diagnostic Medicine&Pathobiology,College of Veterinary Medicine,Kansas State University,Manhattan,KS 66506,USA [2]Division of Animal Sciences,University of Missouri,Columbia,MO 65211,USA [3]Department of Animal Sciences,University of Florida,Gainesville,FL 32611,USA

出　　处：《Animal Diseases》2022年第4期231-245,共15页动物疾病（英文）

基　　金：funded by the National Institutes of Health grant number HD092286(JPD and JAR);the U.S.Department of Agriculture grant number 2016-09448(JPD);the AMP Core of the Center of Emerging and Zoonotic Infectious Diseases(CEZID)from National Institute of General Medical Sciences(NIGMS)under award number P20GM130448;the NIAID supported Centers of Excellence for Infuenza Research and Response(CEIRR,contract number 75N93021C00016;the NIAID funded Center of Excellence for Infuenza Research and Surveillance(CEIRS)grant number HHSN272201400006C(JAR);the U.S.Department of Homeland Security grant number DHS2010-ST-061-AG0001(JAR);the Center of Excellence for Emerging and Zoonotic Animal Disease(CEEZAD).

摘　　要：Natural killer T(NKT)cells activated with the glycolipid ligandα-galactosylceramide(α-GalCer)stimulate a wide variety of immune cells that enhance vaccine-mediated immune responses.Several studies have used this approach to adjuvant inactivated and subunit infuenza A virus(IAV)vaccines,including to enhance cross-protective infuenza immunity.However,less is known about whetherα-GalCer can enhance live attenuated infuenza virus(LAIV)vaccines,which usually induce superior heterologous and heterosubtypic immunity compared to non-replicating infuenza vaccines.The current study used the swine infuenza challenge model to assess whetherα-GalCer can enhance cross-protective immune responses elicited by a recombinant H3N2 LAIV vaccine(TX98ΔNS1)encoding a truncated NS1 protein.In one study,weaning pigs were administered the H3N2 TX98ΔNS1 LAIV vaccine with 0,10,50,and 100μg/kg doses ofα-GalCer,and subsequently challenged with a heterologous H3N2 virus.All treatment groups were protected from infection.However,the addition ofα-GalCer appeared to suppress nasal shedding of the LAIV vaccine.In another experiment,pigs vaccinated with the H3N2 LAIV,with or without 50μg/kg ofα-GalCer,were challenged with the heterosubtypic pandemic H1N1 virus.Pigs vaccinated with the LAIV alone generated cross-reactive humoral and cellular responses which blocked virus replication in the airways,and signifcantly decreased virus shedding.On the other hand,combining the vaccine withα-GalCer reduced cross-protective cellular and antibody responses,and resulted in higher virus titers in respiratory tissues.These fndings suggest that:(i)high doses ofα-GalCer impair the replication and nasal shedding of the LAIV vaccine;and(ii)α-GalCer might interfere with heterosubtypic cross-protective immune responses.This research raise concerns that should be considered before trying to use NKT cell agonists as a possible adjuvant approach for LAIV vaccines.

关 键 词：Natural killer T cell Infuenza A virus Vaccine Live attenuated infuenza virus ADJUVANT α-Galactosylceramide SWINE 

分 类 号：S859.797[农业科学—临床兽医学]