Palivizumab epitope–displaying virus-like particles protect rodents from RSV challenge
Jeanne H. Schickli, … , Gary Van Nest, David R. Milich
Jeanne H. Schickli, … , Gary Van Nest, David R. Milich
Published March 9, 2015
Citation Information: J Clin Invest. 2015;125(4):1637-1647. https://doi.org/10.1172/JCI78450.
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Technical Advance Infectious disease

Palivizumab epitope–displaying virus-like particles protect rodents from RSV challenge

Abstract

Respiratory syncytial virus (RSV) is the most common cause of serious viral bronchiolitis in infants, young children, and the elderly. Currently, there is not an FDA-approved vaccine available for RSV, though the mAb palivizumab is licensed to reduce the incidence of RSV disease in premature or at-risk infants. The palivizumab epitope is a well-characterized, approximately 24-aa helix-loop-helix structure on the RSV fusion (F) protein (F254–277). Here, we genetically inserted this epitope and multiple site variants of this epitope within a versatile woodchuck hepadnavirus core–based virus-like particle (WHcAg-VLP) to generate hybrid VLPs that each bears 240 copies of the RSV epitope in a highly immunogenic arrayed format. A challenge of such an epitope-focused approach is that to be effective, the conformational F254–277 epitope must elicit antibodies that recognize the intact virus. A number of hybrid VLPs containing RSV F254–277 were recognized by palivizumab in vitro and elicited high-titer and protective neutralizing antibody in rodents. Together, the results from this proof-of-principle study suggest that the WHcAg-VLP technology may be an applicable approach to eliciting a response to other structural epitopes.

Authors

Jeanne H. Schickli, David C. Whitacre, Roderick S. Tang, Jasmine Kaur, Heather Lawlor, Cory J. Peters, Joyce E. Jones, Darrell L. Peterson, Michael P. McCarthy, Gary Van Nest, David R. Milich

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Figure 4

VLP-19 protects mice from challenge and elicits nAbs and F-specific IgG.

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VLP-19 protects mice from challenge and elicits nAbs and F-specific IgG....
BALB/c mice (n = 5) were intramuscularly dosed with 100 μl of either 40 μg VLP-19 formulated in IFA or PBS alone on days 0 and 14 or were infected with 106 PFU WT RSV A2 on day 0. On day 28, sera were sampled and mice were challenged with 106 PFU WT RSV A2. On day 32, lungs were harvested. (A) RSV in lung tissue was titered by plaque assay. (B) Heat-inactivated sera were tested for RSV microneutralization titers. (C) Sera were tested by ELISA for sF-specific IgG. This test was performed once with IFA (data shown) and 10 times with GLA-SE, which yielded similar results (data not shown). Data points for each animal are shown, with a black line through the arithmetic mean and colored error bars ± SEM. An unpaired 2-tailed Student’s t test was performed to determine P values. P > 0.05 was considered not significant.