Development and comparison of vsv and mrna vaccines for machupo virus Rachel Erickson

Format:

Book

Thesis/Dissertation

Author/Creator:

Erickson, Rachel, author.

Contributor:

University of Pennsylvania. Cell and Molecular Biology., degree granting institution.

Language:

English

Subjects (All):

Virology.

Molecular biology.

Microbiology.

0720.

0307.

0410.

Local Subjects:

Virology.

Molecular biology.

Microbiology.

0720.

0307.

0410.

Genre:

Academic theses

Physical Description:

1 online resource (142 pages)

Contained In:

Dissertations Abstracts International 87-12B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2026

Language Note:

English

Summary:

Machupo virus (MACV) is a highly pathogenic New World (NW) arenavirus that causes severe hemorrhagic fever and neurologic disease in humans. The overall mortality rate of MACV is around 30% and there are currently no approved treatments or vaccines. Here, we develop four novel vaccines for MACV and test their immunogenicity in mice. Furthermore, we directly compare different vaccine types, each expressing the MACV glycoprotein complex (GPC), to investigate how vaccine platform influences immune response to vaccination. First, we developed recombinant Vesicular stomatitis virus (rVSV)-MACV vaccines expressing the MACV GPC in various genome positions: rVSVs expressing MACV GPC in the first position of the genome (rVSV-MACV1) and in the traditional glycoprotein gene position (rVSV-MACV5). rVSV-MACV1 expresses higher levels of MACV GPC in infected cells and in virions, but the increased antigen does not translate to a more robust immune response. rVSV-MACV5 elicits higher levels of total IgG and neutralizing antibodies than rVSV-MACV1, but similar levels of MACV-specific T cells. Next, we created mRNA-LNP-based vaccines for MACV. The first mRNA-LNP vaccine, MACV mRNA, expresses the full-length MACV GPC. The second mRNA-LNP vaccine, called MACV VLP mRNA, encodes MACV GPC with appended sequences that induce the budding of virus-like particles (VLPs) with MACV GPC on the surface. We found that two doses of either MACV mRNA or MACV VLP mRNA are required for the induction of robust humoral and cellular immune responses including total MACV GPC IgG, neutralizing antibodies, cross-reactive antibodies that bind the related Junín virus GPC, and MACV-specific T-cell responses. To further investigate vaccination strategies for MACV, we also evaluated a heterologous prime-boost regimen involving the MACV mRNA vaccine coupled with the rVSV-based MACV vaccine. We find that the highest levels of MACV GPC-specific IgG and neutralizing titers were achieved when heterologous mRNA and rVSV prime-boost regimens were employed. Overall, this work highlights differences in the immune response to different vaccine platforms for MACV and presents multiple promising vaccine candidates for MACV

Notes:

Source: Dissertations Abstracts International, Volume: 87-12, Section: B.

Advisors: Bates, Paul Committee members: Hensley, Scott; Eisenlohr, Laurence; Jurado, Kellie Ann; Pardi, Norbert

Ph.D. University of Pennsylvania 2026

Vendor supplied data

Local Notes:

School code: 0175

ISBN:

9798247973393

Access Restriction:

Restricted for use by site license