Synthetic Nanoparticle Vaccine Confers Long-Term Protection Against Respiratory Syncytial Virus Infection

A team of molecular virologists and immunologists has shown that alveolar macrophages (AMs) play an important role in immune protection following vaccination against respiratory syncytial virus (RSV) by controlling eosinophils, mucus production, inflammatory cytokines, and T-cell infiltration.

Alveolar macrophages are phagocytes that play a critical role in homeostasis, host defense, the response to foreign substances, and tissue remodeling. Since alveolar macrophages are pivotal regulators of local immunological homeostasis, their population density is decisive for the many processes of immunity in the lungs. They are highly adaptive components of the innate immune system and can be specifically modified to whatever functions needed depending on their state of differentiation and micro-environmental factors encountered. Alveolar macrophages release numerous secretory products and interact with other cells and molecules through the expression of several surface receptors.

Investigators at Georgia State University (Atlanta, USA) studied the role of alveolar macrophages in the immune response mounted by mice that had been vaccinated against RSV with a vaccine comprising either fusion and glycoprotein virus-like nanoparticles (FG VLPs) or formalin-inactivated RSV (FI-RSV). The FG VLP vaccine is currently being evaluated for possible use in humans while the FI-RSV vaccine had been studied and rejected in the 1960s because it caused severe vaccine-enhanced respiratory disease.

In the current study mice were infected with a live RSV pathogen one year after vaccination. In some of the animals the apoptosis-inducing agent clodronate liposomes (CLs) was used to deplete tissue macrophages in order to focus on the role of the alveolar macrophages.

Results published in the July 14, 2015, online edition of the International Journal of Nanomedicine revealed that animals vaccinated with FG VLPs showed no obvious signs of severe pulmonary disease upon RSV infection and displayed significantly lower levels of eosinophils, T-cell infiltration, and inflammatory cytokines. These mice had much higher levels of anti-RSV antibodies and interferon-gamma antiviral cytokine, which are correlated with protection against RSV disease.

In comparison, mice vaccinated with FI-RSV and then treated with clodronate liposomes demonstrated increases in eosinophils, plasmacytoid dendritic cells, interleukin-4 T-cell infiltration, proinflammatory cytokines, chemokines, and mucus production upon RSV infection. FI-RSV immune mice showed severe pulmonary disease in tissue examinations.

The results obtained in this study suggest that FG nanoparticle vaccination induced long-term protection against RSV and that AMs played a role in protection against RSV by modulating eosinophilia, mucus production, inflammatory cytokines, and T-cell infiltration.

"Recombinant engineered nanoparticle vaccines might be developed to prevent highly contagious respiratory pathogens such as RSV, as reported in this study," said senior author Dr. Sang-Moo Kang, professor of biomedical sciences at Georgia State University.

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