Analyzed immunogenicity of fractional doses of Sabin-inactivated poliovirus vaccine (sIPV) with intradermal delivery in rats

Abstract

The live-attenuated oral polio vaccine (OPV) will be no longer used when wild poliovirus (WPV) eliminating in worldwide, according to GPEI (the Global Polio Eradication Initiative) Reports. It is planning to replace OPV by Sabin-based inactivated poliovirus vaccine (sIPV) in developing countries, with purpose of reducing of the economic burden and maintaining of the appropriate antibody levels in population. It studied serial fractional doses immunized by intradermal injection (ID) in rats, to reduce consume of antigen and financial burden, maintaining sufficient immunogenicity; Methods: Study groups were divided in 4 groups of dose gradient, which were one-tenth (1/10), one-fifth (1/5), one-third (1/3) and one-full dose (1/1), according to the volume of distribution taken from the same batch of vaccine (sIPV). Wistar rats were injected intradermally with the needle and syringe sing the mantoux technique taken once month for 3 times. It was used as positive control that intramuscular inoculation (IM) was injected with one-full dose (1/1) with same batch of sIPV. PBS was used as negative control. Blood samples were collected via tail vein. After 30 d with 3 round of immunization, it analyzed the changes of neutralization antibody titers in the each group by each immunization program end; Results: The results of seroconversion had positive correlation with different doses in ID groups. The higher concentration of D-antigen (D-Ag) could conduct higher seroconversion. Furthermore, different types of viruses had different seroconversion trend. It showed that the geometric mean titers (GMTs) of each fractional-dose ID groups increased by higher concentration of D-Ag, and it got significant lower than the full-dose IM group. At 90 days of immunization, the GMTs for each poliovirus subtypes of fractional doses were almost higher than 1:8, implied that it could be meaning positive seroprotection titer for polio vaccine types, according to WHO suggestion; Conclusions: The fractional dose with one-fifth (1/5) could be used by intradermal injection to prevent poliovirus infection, if there were more human clinical detail research consistent with this findings in rats.

Enhanced immunity in intradermal vaccination by novel hollow microneedles

“…Induction of sufficient immune responses by ID delivery of the fractional dose of an existing formulation was encouraging. Since reformulation of existing vaccine needs expensive processes, the present results may facilitate the development of ID delivery as an alternative to SC/IM vaccination.…”

An adjuvant compound that enhances immunogenicity at fractional doses of the Sabin‐inactivated poliovirus vaccine (sIPV) with a long duration of protection in a rat model

“…According to the WHO, the ID route of delivery could reduce the required antigen by 1/5 of the full vaccine . In our previous study, we found that a 1/5 fractional dose could be used by ID injection to prevent poliovirus infection. However, ID delivery might not be suitable for KML05.…”

“…Antibody determination was done by the standard microneutralization technique using Vero cells. The definition of seroconversion rate was consistent with our previous study . Quality‐control requirements were as follows: the serum was heated for half an hour at 56℃ and tested in six steps by twofold dilutions, with a final dilution of 1:320.…”

Analysis of the dose-sparing effect of adjuvanted Sabin-inactivated poliovirus vaccine (sIPV)

“…ID delivery has been proposed as a means to reduce the dose required for vaccination, and it has been shown in several phase 3 trials in infants and adults to be a promising option to dose-spare by 60–80%, despite certain limitations(e.g., dose regimen and age). 10-13 For sIPV, our laboratory conducted pioneering ID tests in rats 14 and found out that the dose could be reduced by 80%, thus, further clinical trials are in preparation. In parallel with ID tests for sIPV, we also seek to determine optimal adjuvants for sIPV.…”