Researchers at Georgia State University say their findings, published July 14 in the International Journal of Nanomedicine, suggest their nanoengineered vaccine induces long-term protection against respiratory syncytial virus (RSV) and could be a novel treatment option for this disease
Researchers at Georgia State University say a vaccine containing virus-like microscopic, genetically engineered particles — i.e.: nanoparticles, has been shown to be an effective treatment for respiratory syncytial virus (RSV).
According to the Centers for Disease Control, RSV is a respiratory virus that infects the lungs and breathing passages, and while healthy people usually experience mild, cold-like symptoms and recover in a week or two, RSV can be serious, especially for infants and older adults. Indeed the CDC notes that RSV is the most common cause of bronchiolitis (inflammation of the small airways in the lung) and pneumonia in children younger than 1 year of age in the United States, with almost all children having been infected with RSV by their second birthday. RSV is additionally is being recognized more often as a significant cause of respiratory illness in older adults.
The Georgia State team’s findings, published July 14 in the International Journal of Nanomedicine, suggest their nanoengineered vaccine induces long-term protection against RSV and could be a novel treatment option for this disease. There is currently no licensed RSV vaccine.
“Recombinant engineered nanoparticle vaccines might be developed to prevent highly contagious respiratory pathogens such as RSV, as reported in this study,” says Dr. Sang-Moo Kang, a professor in the Institute for Biomedical Sciences at Georgia State in a release.
The Open Source paper “Respiratory syncytial virus-like nanoparticle vaccination induces long-term protection without pulmonary disease by modulating cytokines and T-cells partially through alveolar macrophages“ (July 2015 Volume 2015:10 Pages 44914505 DOI http://dx.doi.org/10.2147/IJN.S83493) is coauthored by Young-Tae Lee, Eun-Ju Ko, Hye Suk Hwang, Jong Seok Lee, Ki-Hye Kim, Young-Man Kwon, and Sang-Moo Kang variously of the Center for Inflammation, Immunity and Infection, the Institute for Biomedical Sciences, and the Department of Biology at Georgia State University in Atlanta, Georgia, and the National Institute of Biological Resources, at Incheon, South Korea.
The researchers note that mechanisms of protection against respiratory syncytial virus (RSV) are poorly understood, although virus-like nanoparticles expressing RSV glycoproteins (eg: a combination of fusion and glycoprotein virus-like nanoparticles [FG VLPs]) have been suggested as a potentially promising RSV vaccine candidate.
In order to understand the roles of alveolar macrophages (AMs) in inducing long-term protection, mice that had 12 months earlier been vaccinated with formalin-inactivated RSV (FI-RSV) or FG VLPs were treated with clodronate liposome prior to RSV infection.
In the study, mice were vaccinated with either 1) FG VLPs or virus-like nanoparticles expressing RSV fusion (F) and attachment glycoproteins (G) or 2) FI-RSV or formalin-inactivated RSV, which failed clinical vaccine trials in the 1960s because it caused severe vaccine-enhanced respiratory disease. The mice were infected with live RSV pathogen one year later after vaccination.
Mice vaccinated with FG VLPs showed no obvious sign of severe pulmonary disease in tissue examinations upon RSV infection and significantly lower levels of eosinophils, T-cell infiltration and inflammatory cytokines, but higher levels of antibodies and interferon-g antiviral cytokine, which are correlated with protection against RSV disease.
The investigators report:
“FI-RSV immune mice with clodronate liposome treatment showed increases in eosinophils, plasmacytoid dendritic cells, interleukin (IL)-4+ T-cell infiltration, proinflammatory cytokines, chemokines, and, in particular, mucus production upon RSV infection. In contrast to FI-RSV immune mice with severe pulmonary histopathology, FG VLP immune mice showed no overt sign of histopathology and significantly lower levels of eosinophils, T-cell infiltration, and inflammatory cytokines, but higher levels of interferon— which are correlated with protection against RSV disease. FG VLP immune mice with depletion of AMs showed increases in inflammatory cytokines and chemokines, as well as eosinophils. The results in this study suggest that FG nanoparticle vaccination induces long-term protection against RSV and that AMs play a role in the RSV protection by modulating eosinophilia, mucus production, inflammatory cytokines, and T-cell infiltration.”
The researchers observe that long-term protection against RSV by vaccination is highly desirable, since the elderly are also an RSV target population in addition to young children. However, scientists have been challenged by safety concerns associated with vaccine-enhanced RSV disease as a roadblock to developing effective and safe RSV vaccines. However in this study the researchers found 12 months after vaccinating the mice, that FI-RSV and FG VLP immunization induced long-lasting RSV-specific antibody responses and lowered lung viral loads close to a detection limit upon RSV infection. These findings support the theory that lung viral clearance is largely dependent on RSV antibodies induced by vaccination, with the effective control of lung viral loads in FI-RSV immune mice being consistent with that of previous studies. In this study, the coauthors addressed long-term vaccine safety concerns of FG VLP vaccines and investigated innate and adaptive cellular immune components that are likely responsible for RSV protection or pulmonary inflammation upon RSV infection.
The study suggests recombinant RSV FG virus-like nanoparticle vaccination induces long-term protection against RSV without causing vaccine-enhanced RSV disease by appropriately controlling granulocytes, cytokines and T-cells It also proposes that alveolar macrophages play an important role in RSV protection and innate and adaptive immunity by controlling eosinophils, mucus production, inflammatory cytokines and T-cell infiltration.
However, the scientists also caution that while general features of FI-RSV vaccine-enhanced disease as represented by pulmonary histopathology in humans can be recapitulated in mice, detailed pathological features of RSV disease appear to be different in mice and humans, with nave mice less permissive to RSV infection and disease and requiring high RSV challenge doses in order to achieve significant lung viral loads. They note that severe histopathology and eosinophilia in FI-RSV immune mice despite lung viral clearance were obvious in mice, but it is not known whether these same pathological parameters happen in humans.
Infection of unimmunized nave mice with RSV usually does not induce severe lung histopathology since mice are not highly permissive to RSV, and in this study the investigators observed a substantial degree of lung histopathology in nave mice after RSV infection probably due to the nature of one-year-old aged mice and high lung viral loads. FI-RSV and FG VLP immune mice as well as live RSV previously infected mice were found to be highly effective in controlling lung viral loads by lowering 500- to 1,000-fold.
This work was supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases of the National Institutes of Health grants AI105170, AI093772, and AI119366, to Sang-Moo Kang
For a copy of the study, visit:
Georgia State University
Centres for Disease Control
International Journal of Nanomedicine
Georgia State University