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10/20/18 2:45 PM

#10021 RE: Staypositive1 #10018

Aventis Pasteur, new name of Pasteur Mérieux now Sanofi

Pg 11

ALVAC-HIV - a recombinant Canarypox-vectored vaccine expressing HIV-1 envelope glycoprotein gp120 (subtype E, predominant in

Thailand)

linked to the transmembrane portion of

gp41

and HIV-1 gag and protease (subtype B) produced by

Pasteur Merieux, given at 0, 4, 12 and 24 weeks

RV144 study BRO

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10/20/18 3:27 PM

#10022 RE: Staypositive1 #10018

Among the conserved neutralizing epitopes of Env the Membrane-Proximal External Region (MPER) of gp41 is widely recognized as a promising target for vaccine development.

pg 53 & 54

Sylvain Fleury, Mymetics Corporation, Epalinges, Switzerland


The ideal vaccine to prevent sexual transmission of HIV-1 should obviate entry and
very early infection of HIV-1 at mucosal sites, otherwise it may be too late.
The Mymetics approach is to construct a virosome particle consisting of HIV proteins
embedded in influenza membranes. This looks like a VLP particle in size and the lipid
may improve the antigen presentation. The antigens incorporated are from gp41 and
a Membrane-Proximal External Region (MPER) peptide called P1. P1 is a lipopeptide
Proceedings of the Tenth Global Vaccine Research Forum and Parallel Satellite Symposia, Geneva, 26-29 June 2011
54
containing the Membrane-Proximal External Region (MPER) and the galactosyl
ceramide mucosal receptor binding motif.
The group previously demonstrated that mucosal IgAs/IgGs induced by vaccination
with those virosomes, protect non-human primates (NHP) against vaginal heterologous
SHIV challenges, in the absence of serum neutralizing antibodies. At present they are
investigating if mucosal antibodies with similar antiviral properties can be induced in
women during a Phase I trial. The design is injecting virosomes IM at 0 and 8 weeks,
followed by IN immunization at 16 and 24 wks.
Preliminary results show safety of the virosomes. The immunogenicity results are also
confirming the previous data obtained on non-human primates, and the anti-HIV-1
mucosal responses elicited are an indication of the potential of this approach.

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10/20/18 5:03 PM

#10023 RE: Staypositive1 #10018

LVAC-HIV (vCP2438) is a preparation of live attenuated recombinant canarypox-derived virus expressing products from the HIV-1 env gp120 (subtype C ZM96 [based on HIV-1 96ZM651]), the transmembrane region of env

gp41

, gag, and protease (all subtype B HIV-1 LAI) coding sequences, and cultured in primary chicken embryo fibroblasts. The recombinant canarypox backbone vector used in ALVAC-HIV (vCP2438) was the same as that used for vCP1521 in the RV144 vaccine regimen, but the CRF01_AE gp120 insert (92TH023) was exchanged for a subtype C gp120 insert (96ZM651)

Subtype C ALVAC-HIV and bivalent subtype C gp120/MF59 HIV-1 vaccine in low-risk, HIV-uninfected, South African adults: a phase 1/2 trial

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028742/

Note that they ref

Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia.

https://www.ncbi.nlm.nih.gov/pubmed/18842730

ALVAC is Sanofi's

http://www.sanofipasteur.ca/ckfinder/userfiles/files/Fact_sheet_HIV_ALVAC_EN_tcm28-26355(1).pdf

newer vaccine called ALVAC (delivered in a disabled canarypox virus). Together, the dual vaccines provided the first evidence of significant protection in non-infected people.
Sadly, the RV144 and subsequent RV305 trials proved that the effect was short-lived, declining from a rate of 60 percent by 12 months to 31 percent by 42 months.
With that said, specific immune responses from the ALVAC vaccine proved so compelling that a new study, called the HVTN702 or Uhambo (Zulu for "Journey") trial, is currently underway in South Africa. The aim of the study is to test the efficacy of the ALVAC vaccine in preventing HIV when combined with a gp120 vaccine booster.
The phase IIb/III trial, underway since November 2016, included 5,400 non-infected men and women. The ALVAC will be delivered in an initial intramuscular injection followed by a booster 12 months later. Results are expected by 2020.

https://www.verywellhealth.com/mosaic-hiv-vaccine-sparks-hope-4173079