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Penkert RR, Chandramouli S, Dormitzer PR, et al. Novel Surrogate Neutralizing Assay Supports Parvovirus B19 Vaccine Development for Children with Sickle Cell Disease. Vaccines (Basel). 2021;9(8)doi: 10.3390/vaccines9080860.
Penkert, R. R., Chandramouli, S., Dormitzer, P. R., Settembre, E. C., Sealy, R. E., Wong, S., Young, N. S., Sun, Y., Tang, L., Cotton, A., Dowdy, J., Hayden, R. T., Hankins, J. S., & Hurwitz, J. L. (2021). Novel Surrogate Neutralizing Assay Supports Parvovirus B19 Vaccine Development for Children with Sickle Cell Disease. Vaccines, 9(8), . https://doi.org/10.3390/vaccines9080860
Penkert, Rhiannon R, et al. "Novel Surrogate Neutralizing Assay Supports Parvovirus B19 Vaccine Development for Children with Sickle Cell Disease." Vaccines vol. 9,8 (2021). doi: https://doi.org/10.3390/vaccines9080860
Penkert RR, Chandramouli S, Dormitzer PR, Settembre EC, Sealy RE, Wong S, Young NS, Sun Y, Tang L, Cotton A, Dowdy J, Hayden RT, Hankins JS, Hurwitz JL. Novel Surrogate Neutralizing Assay Supports Parvovirus B19 Vaccine Development for Children with Sickle Cell Disease. Vaccines (Basel). 2021 Aug 04;9(8). doi: 10.3390/vaccines9080860. PMID: 34451986; PMCID: PMC8402426.
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Vaccines (Basel). 2021 Aug 04;9(8). doi: 10.3390/vaccines9080860.

Novel Surrogate Neutralizing Assay Supports Parvovirus B19 Vaccine Development for Children with Sickle Cell Disease.

Vaccines

Rhiannon R Penkert, Sumana Chandramouli, Philip R Dormitzer, Ethan C Settembre, Robert E Sealy, Susan Wong, Neal S Young, Yilun Sun, Li Tang, Alyssa Cotton, Jola Dowdy, Randall T Hayden, Jane S Hankins, Julia L Hurwitz

Affiliations

  1. Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  2. Novartis Vaccines and Diagnostics, Cambridge, MA 02139, USA.
  3. Hematology Branch, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
  4. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  5. Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  6. Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
  7. Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

PMID: 34451986 PMCID: PMC8402426 DOI: 10.3390/vaccines9080860

Abstract

Children with sickle cell disease (SCD) suffer life-threatening transient aplastic crisis (TAC) when infected with parvovirus B19. In utero, infection of healthy fetuses may result in anemia, hydrops, and death. Unfortunately, although promising vaccine candidates exist, no product has yet been licensed. One barrier to vaccine development has been the lack of a cost-effective, standardized parvovirus B19 neutralization assay. To fill this void, we evaluated the unique region of VP1 (VP1u), which contains prominent targets of neutralizing antibodies. We discovered an antigenic cross-reactivity between VP1 and VP2 that, at first, thwarted the development of a surrogate neutralization assay. We overcame the cross-reactivity by designing a mutated VP1u (VP1uAT) fragment. A new VP1uAT ELISA yielded results well correlated with neutralization (Spearman's correlation coefficient = 0.581;

Keywords: VP1u; aplastic crisis; enzyme-linked immunosorbent assay; neutralization assay; parvovirus B19; sickle cell disease; vaccine

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