BIOLOGICAL MIMETICS, INC. — Department of Health and Human Services SBIR Phase II: NIAID

Description

AbstractAfter decades of effortglobal campaigns to eradicate poliovirus are nearing completionEradiation of wild type PVhas been certified and PVand PVmay be eradicated in the next few yearsMany organizations and countries have collaborated in these efforts and are to be congratulated for their dedication and persistenceThe oral polio vaccineOPVhas been the workhorse of mass vaccination efforts because of its low cost and ability to stimulate robust and durable immunityHoweverOPV quickly reverts to pathogenic phenotypes in the human and vaccinees secrete wild type virus that can infect na ve bystandersIn additionthe virus can replicate chronically in immune compromised people who can shed virus for many yearsFor these reasonsOPV is being replaced by the inactivated polio vaccineIPVwhich also stimulates durable immunityUnfortunatelyIPV costs considerably more than OPV per dose$vs $on the subsidized world marketBecause the WHO and most countries have plans to continue vaccination for at leastyears after eradicationthere will continue to be a market for the vaccineBecause of the high cost of the IPVefforts are underway to derive improved and less expensive IPV vaccinesIn a PhaseSBIRwe tested the feasibility of producing a less expensive IPV using a recently developed radiation inactivation methodA reconstituted Mndecapeptide phosphate complexMDPfrom the radiation resistant bacterium Deinococcus radiodurans protects antigenic sites in proteins from oxidative damage at radiation doses that obliterate DNA RNA genomes of viral and bacterial pathogensWe hypothesized that the new method could increase the antigenicity per unit of starting virus because it avoids the extensiveday formalin incubation that damages the polio antigens by spontaneous protein degradation and cross linking epitopesPreservation of antigenicity would increase the number of doses that can be produced per milligram of purified virus and simplification of the inactivation process could reduce costs furtherAfter optimizing the process for inactivatingof virus infectivity while protecting the protein capsidwe normalized the irradiated PVvirus to the D antigen concentrations found in commercial vaccinesRats immunized with irradiated PVdeveloped robust neutralizing titersAfraction of the normal human dose of irradiated PVstimulated similar levels of neutralizing antibodies as aX dose of the commercial IPV productWe propose to extend these findings to include PVand PVand then derive a trivalent vaccine having the minimum dose of each component that stimulates equivalent neutralizing antibody levels as IPVIn addition to a reduction in costthe novel vaccine will have two additional featuresthe use of attenuated Sabin strains and the development of lyophilization proceduresThe transition to Sabin strains will reduce the biohazard risks currently associated with producing large quantities of pathogenic strainsThis feature may allow less sophisticated companies or government labs in developing countries to manufacture their own vaccinesIn additionthe use of the Sabin strains may improve acceptance of the product due to the reduced risk perception associated with low levels of residual infections virus that may not be detected in quality analysis proceduresThe development of a lyophilization process would improve product stability such that the vaccine would not require refrigeration during shipping and may reduce the need for refrigerated storageIn additiona lyophilized vaccine could be stable for many years when placed in national vaccine stockpilesWe have discussed the findings of the Phase I with several polio vaccine experts and scientists at companies that currently manufacture the vaccineThe results have been met with enthusiasm and interest for future interactionsWe will keep the wider community informed of our progress during the Phase II so that we may have partnering options earlier in the development process than originally plannedThe main goal of the project is to develop an improved and less expensive inactivated polio vaccineHoweverthe project will also advance the irradiation technology using a highly characterized virusThe same method could be applied to the rapid and efficient preparation of vaccines against newly emerging pathogens such as EbolaZikaand other deadly pathogensThe regulatory pathway derived from the development of a radiation inactivated PV vaccine would be invaluable when developing vaccines against these less characterized pathogens