Award Number: W81XWH-18-1-0094 ( found the pdf of
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Posted On: 10/13/2024 8:29:48 PM
Award Number: W81XWH-18-1-0094
( found the pdf of it just now )
TITLE:
A Fetus-Targeted Antibody Therapy to Prevent
Zika Virus Infection During Pregnancy
PRINCIPAL INVESTIGATOR:
Diogo Magnani
REPORT DATE:
MAY 2020
TYPE OF REPORT:
Annual Report
PREPARED FOR:
U.S. Army Medical Research and Materiel Command
Fort Detrick, Maryland 21702-5012
DISTRIBUTION STATEMENT:
Approved for public release; distribution unlimited
4. TITLE AND SUBTITLE
A Fetus-Targeted Antibody Therapy to Prevent Zika Virus Infection During Pregnancy
5b. GRANT NUMBER
W81XWH-18-1-0094
6. AUTHOR(S)
Diogo Magnani
E-Mail: Diogo.Magnani@umassmed.edu
9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES)
U.S. Army Medical Research and Materiel Command
Fort Detrick, Maryland 21702-5012
ABSTRACT
Interventions are urgently needed to prevent the severe fetal complications of Zika virus infection. In the US, one in ten pregnant women infected with Zika virus delivered babies with severe birth defects, including small head size (microcephaly) and other neurological problems. Once the fetus is infected, there is nothing we can do to stop viral replication with current technologies.
An approach considered safe for the fetus is to administer antibodies that can neutralize Zika virus. The problem, however, is that these effective antivirals, cannot reach the fetal tissues early in the pregnancy in sufficient amounts to be effective. Here, we are proposing to engineer antibody molecules so that they will cross the placenta effectively and reach the fetus.
We will test our approach in rhesus monkeys, the best animal model of Zika virus infections during human pregnancy, by administering our fetus-targeted’ antibody to pregnant macaques and challenging with Zika virus.
If the antibodies can indeed prevent fetal infection on macaques, this proposal might lead to one of the first effective therapies for Zika virus infection.
1. INTRODUCTION:
Our ultimate objective is to prevent fetal Zika virus (ZIKV) infection. We are testing a novel approach for
preventing fetal ZIKV replication, by engineering monoclonal antibody (mAb) delivery to the fetus.
The proposed experiments are straightforward: we are engineering a ZIKV-neutralizing antibody with neonatal Fc receptor (FcRn)-enhancing mutations and testing in vitro. The ability of this antibody to cross the placenta and prevent ZIKV infection will be tested in vivo.
Our major goal is, therefore, to define mAb mutations that result in enhanced transplacental transfer of therapeutic monoclonal antibodies.
* We used our DNA vectors to express the ZIKV-neutralizing antibody SMZAb2 in wild-type and mutated
versions to modify the interactions with FcRn.
•We also constructed and expressed our control antibody molecules:
• anti-HIV [F240] as a human antibody
• anti_HIV[CH58R1L] as a rhesus antibody
• anti-Tetanus as a human antibody
• anti-DSP as a rhesus antibody
• anti-HIV [MN215] as a rhesus antibody containing a N297G Fc mutation
• anti-HIV[3D6] as a rhesus antibody containing a LS Fc mutation
___
I'll stop there.
Our FcRn publication is right in-line with this contract.
Same DOD # W81XWH-18-1-0094.
Everything reads as two Zika studies under this DOD contract.
1. Diogo Magnani route 1st.
ART + a MAB.
2. LL-PLS + bNAbs + ART
Control antibody molecules, say --- anti-HIV & this DOD is not vaccine trial(s) for Zika.
Not a medical mind, but we all know LL's HIV record.
& Diogo Magnani designed the stability of LL-PLS.
Now with his Zika ART & MAB data, we move to what Cytodyn has mentioned -- bNAbs + LL-PLS + ART.
Goal reducing or eliminating ART for HIV & Zika.
To me, targeting Zika too @ correct time, is going to happen.
Successful HIV data & the science community will be clamoring for a Zika trial too.
That will compliment the rest of what Cytodyn management has already initiated.
LL-PLS --- worldwide news & household name.
Whichever that ends up being.
( found the pdf of it just now )
TITLE:
A Fetus-Targeted Antibody Therapy to Prevent
Zika Virus Infection During Pregnancy
PRINCIPAL INVESTIGATOR:
Diogo Magnani
REPORT DATE:
MAY 2020
TYPE OF REPORT:
Annual Report
PREPARED FOR:
U.S. Army Medical Research and Materiel Command
Fort Detrick, Maryland 21702-5012
DISTRIBUTION STATEMENT:
Approved for public release; distribution unlimited
4. TITLE AND SUBTITLE
A Fetus-Targeted Antibody Therapy to Prevent Zika Virus Infection During Pregnancy
5b. GRANT NUMBER
W81XWH-18-1-0094
6. AUTHOR(S)
Diogo Magnani
E-Mail: Diogo.Magnani@umassmed.edu
9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES)
U.S. Army Medical Research and Materiel Command
Fort Detrick, Maryland 21702-5012
ABSTRACT
Interventions are urgently needed to prevent the severe fetal complications of Zika virus infection. In the US, one in ten pregnant women infected with Zika virus delivered babies with severe birth defects, including small head size (microcephaly) and other neurological problems. Once the fetus is infected, there is nothing we can do to stop viral replication with current technologies.
An approach considered safe for the fetus is to administer antibodies that can neutralize Zika virus. The problem, however, is that these effective antivirals, cannot reach the fetal tissues early in the pregnancy in sufficient amounts to be effective. Here, we are proposing to engineer antibody molecules so that they will cross the placenta effectively and reach the fetus.
We will test our approach in rhesus monkeys, the best animal model of Zika virus infections during human pregnancy, by administering our fetus-targeted’ antibody to pregnant macaques and challenging with Zika virus.
If the antibodies can indeed prevent fetal infection on macaques, this proposal might lead to one of the first effective therapies for Zika virus infection.
1. INTRODUCTION:
Our ultimate objective is to prevent fetal Zika virus (ZIKV) infection. We are testing a novel approach for
preventing fetal ZIKV replication, by engineering monoclonal antibody (mAb) delivery to the fetus.
The proposed experiments are straightforward: we are engineering a ZIKV-neutralizing antibody with neonatal Fc receptor (FcRn)-enhancing mutations and testing in vitro. The ability of this antibody to cross the placenta and prevent ZIKV infection will be tested in vivo.
Our major goal is, therefore, to define mAb mutations that result in enhanced transplacental transfer of therapeutic monoclonal antibodies.
* We used our DNA vectors to express the ZIKV-neutralizing antibody SMZAb2 in wild-type and mutated
versions to modify the interactions with FcRn.
•We also constructed and expressed our control antibody molecules:
• anti-HIV [F240] as a human antibody
• anti_HIV[CH58R1L] as a rhesus antibody
• anti-Tetanus as a human antibody
• anti-DSP as a rhesus antibody
• anti-HIV [MN215] as a rhesus antibody containing a N297G Fc mutation
• anti-HIV[3D6] as a rhesus antibody containing a LS Fc mutation
___
I'll stop there.
Our FcRn publication is right in-line with this contract.
Same DOD # W81XWH-18-1-0094.
Everything reads as two Zika studies under this DOD contract.
1. Diogo Magnani route 1st.
ART + a MAB.
2. LL-PLS + bNAbs + ART
Control antibody molecules, say --- anti-HIV & this DOD is not vaccine trial(s) for Zika.
Not a medical mind, but we all know LL's HIV record.
& Diogo Magnani designed the stability of LL-PLS.
Now with his Zika ART & MAB data, we move to what Cytodyn has mentioned -- bNAbs + LL-PLS + ART.
Goal reducing or eliminating ART for HIV & Zika.
To me, targeting Zika too @ correct time, is going to happen.
Successful HIV data & the science community will be clamoring for a Zika trial too.
That will compliment the rest of what Cytodyn management has already initiated.
LL-PLS --- worldwide news & household name.
Whichever that ends up being.
(4)
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