Estimating Vaccine Potency Using Antibody-Based Competition Assays

Abstract

The issues of vaccine potency and stability constitute formidable challenges associated with the development and readiness of vaccines for biodefense. In most instances, the vaccines will be stockpiled (at considerable cost) for years and used only in the rare event of a public health emergency. It is therefore imperative that there be means to readily monitor overall stability of the stockpiled vaccines, preferably using reliable in vitro assays, without the need for expensive and labor-intensive animal studies. In this chapter, we describe an in vitro monoclonal antibody-based competition ELISA known as RiCoE for assessing the potency of a ricin toxin subunit vaccine. RiCoE can be applied to drug substance and drug products adsorbed to aluminum salts adjuvant. While RiCoE is specific for ricin toxin, the general methodologies and protocols described herein are amenable to virtually any subunit or even virus-like particle-based vaccine. Ultimately, RiCoE-like assays may replace or at least reduce the need for animal studies in vaccine potency determinations.

Single-domain antibodies reveal unique borreliacidal epitopes on the Lyme disease vaccine antigen, Outer surface protein A (OspA)

“…Identity testing will be especially relevant when evaluating recombinant or nucleic acid-based hexavalent and even heptavalent Lyme disease vaccines (6). We have also described other antibody-based applications for vaccine development that may be pertinent to Lyme disease (53).…”

Serum antibody profiling identifies vaccine-induced correlates of protection against aerosolized ricin toxin in rhesus macaques

“…We next investigated whether EPICC analysis was a possible COP. EPICC is a modified sandwich ELISA in which serum samples from experimental animals are assessed for their ability to inhibit the capture of soluble, biotinylated RT by a panel of immobilized mAbs directed against immunodominant toxin-neutralizing epitopes on RiVax® [23][24][25][26] . We recently reported that EPICC inhibition values constitute a vaccine-induced COP in a mouse model of systemic RT challenge (reproduced in Table 2) 25 .…”

“…Since that original report, we have refined the epitope profiling immuno-competition capture assay (EPICC). In mouse models of parenteral RT exposure following RiVax® vaccination across a range of doses, pre-challenge total RT-specific and EPICC values each correlated with survival [23][24][25][26] . However, it is not known to what degree vaccine-induced RT-specific IgG or EPICC values correlate with protection in the rhesus macaque model.…”