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Prenatal monoclonal antibodies
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neonatal Fc receptor
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https://clinicaltrials.gov/search?cond=neonat...20receptor
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Showing results for: M428L/N434S
Did you mean m281 n434s ?
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m281 n434s
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From our Placenta paper:
" We administered leronlimab-PLS or leronlimab-WT, along with a reference control mAb, in two groups of three pregnant rhesus macaques each and compared the mAb levels transferred into the fetal circulation.
Using this experimental design, we found elevated mAb levels in the fetal compartment in the leronlimab-PLS treatment group compared to the leronlimab-WT group.
Consistent with the higher leronlimab-PLS levels in infant circulation, infants in the group that received leronlimab-PLS maintained higher and prolonged CCR5 receptor occupancy (RO).
Importantly, the differences in mAb transfer were specific to leronlimab, as we observed no variations in the transfer of the control mAb or the native rhesus Abs between the groups.
Our results suggest that engineering mAbs for FcRn-enhancement can be used to optimize fetus-targeted Ab therapies"
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" Our modified version of leronlimab, termed leronlimab-PLS incorporates two sets of mutations: M428L/N434S (LS) for FcRn-IgG enhancement and S228P for core-hinge stabilization."
"The results confirmed the affinity enhancement effects of LS on the binding interaction with rhesus FcRn. Further, the thermal stability profiles ensured that the incorporated mutations on leronlimab-PLS did not render the molecule unstable. Thus, with the aim of improving mAb delivery to the fetus, we proceeded to test the leronlimab-PLS variant in animals."
S228P paper in 2015 & performed as stated, for LL.
https://pubmed.ncbi.nlm.nih.gov/25568323/
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Back to LL-PLS paper quick excerpts.
"Our previous study confirmed that therapeutic mAbs administered to dams antenatally can be transported to fetuses.Citation43 However, the administration of a highly potent antiviral human mAb cocktail to Zika virus-infected pregnant macaques, at the time of peak viremia, was insufficient to block viral replication in the fetal compartment"
Here's the Ai take on mAbs & Zika:
Monoclonal antibodies (mAbs) have been shown to be effective in preventing Zika virus (ZIKV) infection in mice and neutralizing the virus in vitro. However, mAb treatment has been unsuccessful in preventing ZIKV from infecting fetuses in pregnant macaques:
Two mAbs:
In one study, two mAbs were unable to prevent viremia in one pregnant macaque, and the virus crossed the placenta in another.
Three mAbs:
In another study, three mAbs were administered 24 hours before infection, protecting four out of four animals from detectable virus in the blood. However, when administered three days after infection, the virus was still detectable in the amniotic fluid of two out of three animals.
Combination of two engineered mAbs:
In a study, two engineered mAbs (Z004 and Z021) partially protected against fetal neurologic damage and limited vertical transmission of ZIKV. However, the antibodies did not eliminate maternal viremia.
ZIKV infection during pregnancy can cause severe congenital disease, including microcephaly, spontaneous abortion, intrauterine growth restriction, and fetal demise.
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LL-PLS most likely immediate goals of future information:
* HIV
*Rantes
* ZIKA
We know LL outbinds Rantes.
ZIKA is mentioned in alot of studies & LL-PLS is mentioning too, for a reason.
Seeing what LL-PLS outbinds to FcRn, is going to be stunning.
For LL-PLS to safely help protect the origins of life.
Via the 1st organ of the body,
the Placenta.