Induction of Long-Term Protective Immune Responses by Influenza H5N1 Virus-Like Particles

Abstract

BackgroundRecurrent outbreaks of highly pathogenic H5N1 avian influenza virus pose a threat of eventually causing a pandemic. Early vaccination of the population would be the single most effective measure for the control of an emerging influenza pandemic.Methodology/Principal FindingsInfluenza virus-like particles (VLPs) produced in insect cell-culture substrates do not depend on the availability of fertile eggs for vaccine manufacturing. We produced VLPs containing influenza A/Viet Nam1203/04 (H5N1) hemagglutinin, neuraminidase, and matrix proteins, and investigated their preclinical immunogenicity and protective efficacy. Mice immunized intranasally with H5N1 VLPs developed high levels of H5N1 specific antibodies and were 100% protected against a high dose of homologous H5N1 virus infection at 30 weeks after immunization. Protection is likely to be correlated with humoral and cellular immunologic memory at systemic and mucosal sites as evidenced by rapid anamnestic responses to re-stimulation with viral antigen in vivo and in vitro.Conclusions/SignificanceThese results provide support for clinical evaluation of H5N1 VLP vaccination as a public health intervention to mitigate a possible pandemic of H5N1 influenza.

Synthesis of empty african horse sickness virus particles

“…U90337 and P18259, respectively). A crystallographic reconstruction of the top domain of AHSV-4 VP7 (pdb1AHS) was also utilized as structural template to generate homology protein models of the top domain of the wild-type or mutant AHSV-9 VP7 proteins with the ESyPred3D homology modeling program (Lambert et al, 2002). All models were visualized and analyzed with the PyMOL Molecular Graphics System v0.98 (DeLano, 2002).…”

“…These are self-assembling, non-replicating, non-pathogenic synthetic particles that mimic the native virus, as well as contain a diverse, repetitive high-density display of viral epitopes in the native conformation. VLP-based vaccines not only elicit humoral immune responses, but are also effective in stimulating CD4 + proliferative and cytotoxic T lymphocyte (CTL) responses (Grgacic and Anderson, 2006;Kang et al, 2009). These attributes render VLPs safer than the conventional vaccines and superior to recombi-nant single-protein subunit vaccines in eliciting strong, long-lived protective immune responses, even in the absence of adjuvants (Noad and Roy, 2003;Grgaciac and Anderson, 2006).…”

Intradermal Vaccination with Influenza Virus-Like Particles by Using Microneedles Induces Protection Superior to That with Intramuscular Immunization

“…VLPs are an attractive format of vaccine that has been demonstrated to be effective in inducing protective immunity against influenza virus infection (9,15,19,27,35,41,42,44). However, no previous studies have reported vaccination using influenza VLPs in the skin, which is an attractive alternative route of vaccination (5,13,14,22).…”

“…Influenza VLPs are noninfectious particles that mimic the virus in structure and morphology, can be produced using an egg-free cell culture system, and have been shown to be highly immunogenic, inducing protective immunity (9,15,19,27,35,41,42,44). Most current vaccines are administered intramuscularly to humans in liquid formulations using hypodermic needles or syringes.…”

Animal Models of Respiratory Syncytial Virus Pathogenesis and Vaccine Development: Opportunities and Future Directions

“…Licensures of two VLP vaccines (papilloma virus and hepatitis B virus) reflect the potential of VLP vaccines. Viral proteins presented as VLPs are highly immunogenic and induce protective humoral, cellular, and mucosal immune responses (Kang et al, 2009;Quan et al, 2007) Recent studies with Venezuelan equine encephalitis virus replicon particles (VRPs) expressing HRSV G or F as well as HRSV Gexpressing Newcastle disease VLPs suggest that HRSV nonreplicating VLP-like vaccines, even without adjuvants, are immunogenic, effective, and do not cause ERD (Mok et al, 2007;Murawski et al, 2009). These G-and/or F-expressing VLPs lack immunomodulatory NS proteins, so they may less interfere with host immune responses than live attenuated vaccines that do express NS proteins.…”