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An Engineered Biomimetic MPER Peptide Vaccine Induces Weakly HIV Neutralizing Antibodies in Mice

  • Biomaterials - Engineering Cell Behavior
  • Published:
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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.

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Acknowledgments

This work was supported by the National Institutes of Health (R01AI125119, R21AI122964, DP5OD017898, HHSN272201800004C). We would like to thanks Earl Poptic at Cleveland Clinic for hybridoma work. We acknowledge PATH-MVI for providing Pfs25.

Conflict of interest

JF.L and W.H. hold interest in POP Biotechnologies. All other authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Biomedical Engineering, State University of New York at Buffalo, Buffalo, NY, 14260, USA

    Shuai Shao, Wei-Chiao Huang, Cuiyan Lin & Jonathan F. Lovell

  2. The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450018, Henan, China

    Shuai Shao

  3. Department of Surgery, Duke University Medical Center, Durham, NC, USA

    Celia C. LaBranche & David C. Montefiori

  4. Department of Pediatrics, State University of New York at Buffalo, Buffalo, NY, 14214, USA

    Mark D. Hicar

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  1. Shuai Shao
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Correspondence to Jonathan F. Lovell.

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Shao, S., Huang, WC., Lin, C. et al. An Engineered Biomimetic MPER Peptide Vaccine Induces Weakly HIV Neutralizing Antibodies in Mice. Ann Biomed Eng 48, 1991–2001 (2020). https://doi.org/10.1007/s10439-019-02398-8

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  • DOI: https://doi.org/10.1007/s10439-019-02398-8

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