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dc.contributor.authorShoudy, Lauren E
dc.contributor.authorNamjoshi, Prachi
dc.contributor.authorGiordano, Gabriela
dc.contributor.authorKumar, Sudeep
dc.contributor.authorBowling, Jennifer D
dc.contributor.authorGelhaus, Carl
dc.contributor.authorBarry, Eileen M
dc.contributor.authorHazlett, Allan J
dc.contributor.authorHazlett, Brian A
dc.contributor.authorCooper, Kristine L
dc.contributor.authorPittman, Phillip R
dc.contributor.authorReed, Douglas S
dc.contributor.authorHazlett, Karsten R O
dc.date.accessioned2022-01-19T16:21:03Z
dc.date.available2022-01-19T16:21:03Z
dc.date.issued2021-12-20
dc.identifier.urihttp://hdl.handle.net/10713/17606
dc.description.abstractIdentifying correlates of protection (COPs) for vaccines against lethal human (Hu) pathogens, such as Francisella tularensis (Ft), is problematic, as clinical trials are currently untenable and the relevance of various animal models can be controversial. Previously, Hu trials with the live vaccine strain (LVS) demonstrated ~80% vaccine efficacy against low dose (~50 CFU) challenge; however, protection deteriorated with higher challenge doses (~2000 CFU of SchuS4) and no COPs were established. Here, we describe our efforts to develop clinically relevant, humoral COPs applicable to high-dose, aerosol challenge with S4. First, our serosurvey of LVS-vaccinated Hu and animals revealed that rabbits (Rbs), but not rodents, recapitulate the Hu O-Ag dependent Ab response to Ft. Next, we assayed Rbs immunized with distinct S4-based vaccine candidates (S4ΔclpB, S4ΔguaBA, and S4ΔaroD) and found that, across multiple vaccines, the %O-Ag dep Ab trended with vaccine efficacy. Among S4ΔguaBA-vaccinated Rbs, the %O-Ag dep Ab in pre-challenge plasma was significantly higher in survivors than in non-survivors; a cut-off of >70% O-Ag dep Ab predicted survival with high sensitivity and specificity. Finally, we found this COP in 80% of LVS-vaccinated Hu plasma samples as expected for a vaccine with 80% Hu efficacy. Collectively, the %O-Ag dep Ab response is a bona fide COP for S4ΔguaBA-vaccinated Rb and holds significant promise for guiding vaccine trials with higher animals.en_US
dc.description.urihttps://doi.org/10.3390/pathogens10121646en_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofPathogens (Basel, Switzerland)en_US
dc.subjectFrancisellaen_US
dc.subjectO-Antigenen_US
dc.subjectanimal modelsen_US
dc.subjecthumansen_US
dc.subjectrabbitsen_US
dc.subjectrodentsen_US
dc.titleThe O-Ag Antibody Response to Francisella Is Distinct in Rodents and Higher Animals and Can Serve as a Correlate of Protection.en_US
dc.typeArticleen_US
dc.identifier.doi10.3390/pathogens10121646
dc.identifier.pmid34959601
dc.source.journaltitlePathogens (Basel, Switzerland)
dc.source.volume10
dc.source.issue12
dc.source.countryUnited States
dc.source.countrySwitzerland


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