Deleterious effect of thimerosal on the potency of inactivated poliovirus vaccine.
High-potency inactivated poliovirus vaccine (eIPV) was combined with diphtheria-tetanus-pertussis (DTP) vaccine containing thimerosal as a preservative to simulate the performance of a potential tetravalent vaccine. Neither type 1 nor type 3 poliovirus antigens appeared to be affected by thimerosal after exposure for 1 h at 37 degrees C as measured by enzyme-linked immunosorbent assay (ELISA). One epitope on the type 2 antigen was damaged within 5 min of exposure; however, the overall potency was unchanged when measured using a polyclonal antibody preparation. Exposure to thimerosal at 37 degrees C decreased the potency of all three poliovirus types to well below the level caused by heat deterioration alone in 1-2 days and to 0% after 16-17 days. At 25 degrees C, the potency of type 1 poliovirus decreased by 46% in 1 day, whereas poliovirus types 2 and 3 were stable for 1 week. Storage of eIPV at 4 degrees C in the presence of thimerosal reduced the potency of type 1 poliovirus antigen to undetectable levels after 4-6 months. Type 2 and 3 antigens were less markedly affected by 8 months of exposure to thimerosal at 4 degrees C. The loss of potency of type 1 as measured by ELISA was paralleled by a reduced level of neutralizing antibodies in mice injected with these preparations. The results obtained from testing eIPV in combination with DTP and thimerosal were generally similar to those obtained using eIPV with thimerosal. It remains to be seen to what extent thimerosal will affect the immunogenicity of eIPV in humans when injected as combined eIPV-DTP vaccine.
Sawyer
L A
LA
Laboratory of Pediatric Diseases, Food and Drug Administration, Bethesda, MD.
McInnis
J
J
Patel
A
A
Horne
A D
AD
Albrecht
P
P
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000956:Antigens, Viral / Q000187:drug effects* / Q000276:immunology; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000737:chemistry / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000187:drug effects; D005260:Female; D006358:Hot Temperature; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011054:Poliovirus Vaccine, Inactivated / Q000276:immunology / Q000592:standards*; D013047:Specific Pathogen-Free Organisms; D013849:Thimerosal / Q000494:pharmacology*; D015164:Vaccines, Inactivated / Q000276:immunology / Q000592:standards
D000914:Antibodies, Viral; D000956:Antigens, Viral; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D000939:Epitopes; D011054:Poliovirus Vaccine, Inactivated; D015164:Vaccines, Inactivated; D013849:Thimerosal