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; p = 0.001), superior to results from a standard clinical diagnostic ELISA or an ELISA with virus-like particles. Virus-specific antibodies from children with TAC, measured by the VP1uAT and neutralization assays, but not other assays, gradually increased from days 0 to 120 post-hospitalization. We propose that this novel and technically simple VP1uAT ELISA might now serve as a surrogate for the neutralization assay to support rapid development of a parvovirus B19 vaccine.
Highlights
B19 threatens fetal viability when infections occur during ising new candidates
The second VLP was comprised of only VP2. We found that both VLPs elicited antibodies that bound the VP1mut/VP2 VLP in an ELISA, but only the VP1mut/VP2 VLP elicited detectable neutralizing antibodies
IgG that bound VP1/VP2 VLPs in ELISAs and neutralization
Summary
Parvovirus B19 usually does not cause serious disease in healthy individuals, but in patients with sickle cell disease (SCD), it can cause transient aplastic crisis (TAC), which can Vaccines 2021, 9, 860. Parvovirus B19 usually does not cause serious disease in healthy individuals, b patients with sickle cell disease (SCD), it can cause transient aplastic crisis (TAC), w can lead to permanent organ damage and death [1,2,3,4,5,6,7]. Pa virus B19 threatens fetal health and viability when infections occur during pregna lead to permanent organ damage and death [1,2,3,4,5,6,7]. Licensed vaccine for parvovirus althoughisthere are promiscomposed of two [8,9].
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