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Open Access Research

An adjuvanted respiratory syncytial virus fusion protein induces protection in aged BALB/c mice

Anu Cherukuri1, Kate L Stokes23, Kathryn Patton1, Howard Kuo1, Kaori Sakamoto4, Stacie Lambert1, Elizabeth Stillman1, Martin L Moore23 and Sujin Lee23*

Author Affiliations

1 Infectious Diseases/Vaccines Research, MedImmune, LLC, Mountain View, CA, USA

2 Department of Pediatrics, Emory Children’s Center, Emory University, Atlanta, GA, USA

3 Children’s Healthcare of Atlanta, Atlanta, GA, USA

4 Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA

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Immunity & Ageing 2012, 9:21  doi:10.1186/1742-4933-9-21

Published: 2 October 2012

Abstract

Background

Respiratory Syncytial Virus (RSV) causes significant disease in the elderly, in part, because immunosenescence impairs protective immune responses to infection in this population. Despite previous and current efforts, there is no RSV vaccine currently licensed in infants or elderly adults. Adjuvanted RSV subunit vaccines have the potential to boost waning immune responses and reduce the burden of RSV disease in the elderly population.

Results

We used an aged BALB/c mouse model to evaluate immune responses to RSV Fusion (F) protein in the absence and presence of an alum adjuvant. We demonstrate that aged BALB/c mice immunized with alum-adjuvanted RSV F protein had significantly reduced lung viral titers at day 4 following challenge with wild-type (wt) RSV. Serum neutralizing antibody titers measured on day 27 correlated with protection in both young and aged vaccinated mice, although the magnitude of antibody titers was lower in aged mice. Unlike young mice, in aged mice, alum-adjuvanted RSV F did not induce lung TH2-type cytokines or eosinophil infiltration compared to non-adjuvanted F protein following wt RSV challenge.

Conclusion

Our studies demonstrate that neutralizing anti-RSV antibody titers correlate with protection in both young and aged BALB/c mice vaccinated with RSV F protein vaccines. The F + alum formulation mediated greater protection compared to the non-adjuvanted F protein in both young and aged mice. However, while alum can boost F-specific antibody responses in aged mice, it does not completely overcome the reduced ability of a senescent immune system to respond to the RSV F antigen. Thus, our data suggest that a stronger adjuvant may be required for the prevention of RSV disease in immunosenescent populations, to achieve the appropriate balance of protective neutralizing antibodies and effective TH1-type cytokine response along with minimal lung immunopathology.

Keywords:
Respiratory Syncytial Virus; Immunosenescence; Alum; Adjuvant; Aged mice