Abstract:
:A vaccine that induces broadly neutralizing antibodies (bnAbs) against the human immunodeficiency virus (HIV) would be instrumental in controlling the disease. The membrane proximal external region (MPER) peptide is an appealing antigen candidate since it is conserved and is the target of several human bnAbs, such as 2F5. We previously found that liposomes containing cobalt porphyrin-phospholipid (CoPoP) can bind to a his-tagged MPER peptide, resulting in biomimetic antigen presentation on a lipid bilayer. The present study generated various his-tagged, synthetic MPER fragments, which were bound to liposomes containing CoPoP and a synthetic monophosphoryl lipid A (MPLA) and assessed for immunogenicity in mice. MPER peptides with amino acids stretches originating from the membrane insertion point that were at least 25 amino acids in length, had greater 2F5 reactivity and induced stronger antibody responses, compared to shorter ones. Immunization with the lipid-presented MPER elicited stronger antibody responses compared to Alum and Montanide adjuvants, which could recognize recombinant gp41 and gp140 proteins that contained MPER sequences. The induced antibodies neutralized a tier 1A virus that is sensitive to neutralizing antibodies (W61D(TCLA)0.71), but not another tier 1A nor a tier 2 strain. Co-formulation of the MPER peptide with an unrelated malaria protein antigen (Pfs25) that is effectively adjuvanted with liposomes containing CoPoP and MPLA resulted in elicitation of higher MPER antibody levels, but did not improve neutralization, possibly due to interference with proper peptide presentation in the membrane. Murine hybridomas were generated that produced MPER antibodies, but they were non-neutralizing. These results do not show that bnAbs could be generated with MPER peptides and CoPoP liposomes, but do not rule out this possibility with additional improvements to the approach.
journal_name
Ann Biomed Engjournal_title
Annals of biomedical engineeringauthors
Shao S,Huang WC,Lin C,Hicar MD,LaBranche CC,Montefiori DC,Lovell JFdoi
10.1007/s10439-019-02398-8subject
Has Abstractpub_date
2020-07-01 00:00:00pages
1991-2001issue
7eissn
0090-6964issn
1573-9686pii
10.1007/s10439-019-02398-8journal_volume
48pub_type
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journal_title:Annals of biomedical engineering
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journal_title:Annals of biomedical engineering
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journal_title:Annals of biomedical engineering
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journal_title:Annals of biomedical engineering
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journal_title:Annals of biomedical engineering
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abstract::Cochlear implantation consists in electrically stimulating the auditory nerve by inserting an electrode array inside the cochlea, a bony structure of the inner ear. In the absence of any visual feedback, the insertion results in many cases of damages of the internal structures. This paper presents a feasibility study ...
journal_title:Annals of biomedical engineering
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journal_title:Annals of biomedical engineering
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journal_title:Annals of biomedical engineering
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journal_title:Annals of biomedical engineering
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