A novel combination of intramuscular vaccine adjuvants,nanoemulsion and CpG produces an effective immune response against influenza A virus |
| |
| Institution: | 1. Michigan Nanotechnology Institute for Medicine and Biological Sciences, Michigan Medicine, University of Michigan, Ann Arbor, MI, United States;2. BlueWillow Biologic, Ann Arbor, MI, United States |
| |
| Abstract: | BackgroundVaccination is the most effective approach to prevent infection with highly pathogenic avian influenza (HPAI). Adjuvants are often used to induce effective immune responses and overcome the immunological weakness of recombinant HPAI antigens. Given the logistical challenges of immunization to HPAI during pandemic situations, vaccines administered via the intramuscular (I.M.) route would be of value.MethodsA new formulation of nanoemulsion adjuvant (NE02) suitable for I.M. vaccination was developed. This NE02 was evaluated alone and in combination with CpG to develop H5 immune responses in mouse and ferret models. Measures of recombinant H5 (rH5) specific immunity evaluated included serum IgG and IgG subclasses, bronchoalveolar lavage fluid IgA, and cytokines. The activation of NF-kB was also analyzed. The efficacy of the vaccine was assessed by performing hemagglutination inhibition (HAI), virus neutralization (VN) assays, and viral challenges in ferrets.ResultsI.M. vaccination with rH5-NE02 significantly increased rH5-specific IgG and protected ferrets in the viral challenge model providing complete protection and sterile immunity in all animals tested. Combining NE02 and CpG produced accelerated antibody responses and this was accompanied by an elevation of IFN-γ and IL-17 responses and the downregulation of IL-5. The combination also caused a synergistic effect on NF-kB activation. In immunized ferrets after viral challenge, the rH5-NE02 + CpG vaccine via I.M. achieved at least 75% and 88% seroconversion of HAI and VN antibody responses, respectively, and improved body temperature stabilization and weight loss over NE02 alone.ConclusionsThe I.M. injection of NE02 adjuvanted rH5 elicits strong and broad immune responses against H5 antigens and effectively protects animals from lethal H5 challenge. Combining this adjuvant with CpG enhanced immune responses and provided improvements in outcomes to viral challenge in ferrets. The results suggest that combinations of adjuvants may be useful to enhance H5 immune responses and improve protection against influenza infection. |
| |
| Keywords: | Intramuscular adjuvant Nanoemulsion CpG Influenza A virus Ferret BAL"} {"#name":"keyword" "$":{"id":"k0035"} "$$":[{"#name":"text" "_":"bronchoalveolar lavage fluid (ODN) CpG ODN"} {"#name":"keyword" "$":{"id":"k0045"} "$$":[{"#name":"text" "_":"CpG oligonucleotides ELISpot"} {"#name":"keyword" "$":{"id":"k0055"} "$$":[{"#name":"text" "_":"enzyme-linked immunospot HAI"} {"#name":"keyword" "$":{"id":"k0065"} "$$":[{"#name":"text" "_":"hemagglutination inhibition HA"} {"#name":"keyword" "$":{"id":"k0075"} "$$":[{"#name":"text" "_":"hemagglutinin HPAI"} {"#name":"keyword" "$":{"id":"k0085"} "$$":[{"#name":"text" "_":"highly pathogenic avian influenza Ig"} {"#name":"keyword" "$":{"id":"k0095"} "$$":[{"#name":"text" "_":"immunoglobulins I M "} {"#name":"keyword" "$":{"id":"k0105"} "$$":[{"#name":"text" "_":"intramuscular I N "} {"#name":"keyword" "$":{"id":"k0115"} "$$":[{"#name":"text" "_":"intranasal MDCK"} {"#name":"keyword" "$":{"id":"k0125"} "$$":[{"#name":"text" "_":"Madin-Darby canine kidney NE01"} {"#name":"keyword" "$":{"id":"k0135"} "$$":[{"#name":"text" "$$":[{"#name":"__text__" "_":"nanoemulsion W"} {"#name":"inf" "$":{"loc":"post"} "_":"80"} {"#name":"__text__" "_":"5EC NE02"} {"#name":"keyword" "$":{"id":"k0145"} "$$":[{"#name":"text" "_":"nanoemulsion DODAC NEs"} {"#name":"keyword" "$":{"id":"k0155"} "$$":[{"#name":"text" "_":"nanoemulsions rH5"} {"#name":"keyword" "$":{"id":"k0165"} "$$":[{"#name":"text" "_":"recombinant H5 SFC"} {"#name":"keyword" "$":{"id":"k0175"} "$$":[{"#name":"text" "_":"spot-forming cells 50% tissue culture infective dose VN"} {"#name":"keyword" "$":{"id":"k0195"} "$$":[{"#name":"text" "_":"virus neutralization |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
