Scientific Publications by FDA Staff

J Infect Dis 2004 Oct 15;190(8):1404-12

Evaluation of immunogenicity and protective properties of inactivated poliovirus vaccines: a new surrogate method for predicting vaccine efficacy.

Dragunsky EM, Ivanov AP, Wells VR, Ivshina AV, Rezapkin GV, Abe S, Potapova SG, Enterline JC, Hashizume S, Chumakov KM

Dragunsky EM, HFM-470,NLRC-B-121,1401 Rockville Pike, Rockville, MD 20852 USA US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA Japan Poliomyelitis Res Inst, Tokyo, Japan

An assay for the evaluation of protective properties of inactivated poliovirus vaccines (IPVs) in transgenic (Tg) mice susceptible to poliovirus has been developed and optimized for type 2 IPV. This method was used to compare the immunogenicity and protective properties of experimental IPV produced from the attenuated Sabin strain (sIPV) with those of conventional IPV (cIPV) produced from the wild-type (wt) poliovirus MEF-1 strain. Modified enzyme-linked immunosorbent assays (ELISAs) were used to measure immune response in serum and saliva samples from test mice. Tg mice were vaccinated and were challenged either with wt poliovirus or virulent poliovirus derived from the vaccine strain. Compared with cIPV, sIPV induced lower levels of antibodies and did not completely protect mice against challenge with wt virus but did protect mice against challenge with the virulent vaccine-derived strain. This may be due to an 18% nucleotide difference between the MEF-1 and Sabin 2 strains, resulting in 72 amino acid substitutions and leading to antigenic dissimilarity. Immunological properties of both strains, revealed by cross-neutralization tests and ELISAs, confirmed that MEF-1 possesses broader immunogenicity than does Sabin 2. This animal model may be used for the assessment of new IPVs and of combination vaccines containing an IPV component.