Antibody affinity maturation is a critical step in development of functional antiviral immunity, however, accurate measurement of affinity maturation of polyclonal serum antibody responses to particulate antigens such as virions is challenging. We describe a novel avidity assay employing bio-layer interferometry and dengue virus-like particles. After validation using anti-dengue monoclonal antibodies, the assay was used to assess avidity of antibody responses to a tetravalent dengue vaccine candidate (TAK-003) in children, adolescents and adults during two Phase 2 clinical trials conducted in dengue endemic regions. Vaccination increased avidity index and avidity remained high through one-year post vaccination. Neutralizing antibody titers and avidity index did not correlate overall, however, a correlation was observed between neutralizing antibody titer and avidity index in those subjects with the highest degree of antibody affinity maturation. Therefore, vaccination with TAK-003 stimulates polyclonal affinity maturation and functional antibody responses including neutralizing antibodies.
An oil-based formulation of the EG95 vaccine to protect grazing animals against infection with Echinococcus granulosus was formulated in Argentina. The efficacy of the vaccine was monitored by serology in sheep and llama (Lama glama) and was compared to the serology in sheep previously published using a QuilA-adjuvanted vaccine. Long-term efficacy was also tested in sheep by challenging with E. granulosus eggs of the G1 strain 4 years after the beginning of the trial. The serological results for both sheep and llama were similar to those described previously, except that there was a more rapid response after the first vaccination. A third vaccination given after 1 year resulted in a transient boost in serology that lasted for about 12 months, which was similar to results previously described. Sheep challenged after 4 years with three vaccinations presented 84·2% reduction of live cysts counts compared with control group, and after a fourth vaccination prior to challenge, this reduction was 94·7%. The oil-based vaccine appeared to be bio-equivalent to the QuilA vaccine.
An effective dengue vaccine should ideally induce broadly neutralizing antibody (nAb) responses against all four dengue virus (DENV) serotypes. We characterized the specificity and breadth of the nAb response to TAK-003, a live attenuated tetravalent dengue vaccine, in serum samples from phase 2 and 3 clinical trials. Microneutralization tests using post-vaccination serum showed comparable neutralization against diverse DENV-1−4 genotypes. Reporter virus particle neutralization assays post- depletion of anti-DENV-2 nAbs demonstrated that the nAb response to DENV-1, -3 and -4 comprises both type-specific (TS) and cross-reactive (CR) nAbs. Therefore, TAK-003 induces broad tetravalent TS and CR nAb responses.
ZIKV is a global health concern against which no vaccine or therapeutics are available. We characterized eight novel rabbit monoclonal antibodies recognizing ZIKV envelope and prM proteins and studied the relationship between somatic hypermutation of complementarity-determining regions, framework regions, mutations, antibody specificity, binding, and neutralizing activity.
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