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Broadly neutralizing antibodies against pandemic pathogens lessons for vaccine and therapeutic design Ashwin Nicholas Skelly
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Skelly, Ashwin Nicholas, author.
- Language:
- English
- Subjects (All):
- Immunology.
- Virology.
- Medicine.
- Clinical psychology.
- 0982.
- 0720.
- 0564.
- 0622.
- Local Subjects:
- Immunology.
- Virology.
- Medicine.
- Clinical psychology.
- 0982.
- 0720.
- 0564.
- 0622.
- Genre:
- Academic theses
- Physical Description:
- 1 online resource (208 pages)
- Contained In:
- Dissertations Abstracts International 87-12B
- Place of Publication:
- Ann Arbor : ProQuest Dissertations and Theses, 2026
- Language Note:
- English
- Summary:
- Vaccines against evolving pathogens such as HIV-1 and SARS-CoV-2 will need to induce broadly neutralizing antibodies (bNAbs) to protect against current and future viral variants. Isolation and characterization of bNAbs that recognize conserved epitopes on the viral fusion machinery can inform the design of novel immunogens and enable the development of monoclonal antibody therapeutics. Here, we established an outbred macaque model of consistent HIV bNAb induction using a simian-human immunodeficiency virus (SHIV) bearing an Envelope that selectively exposes the V3-glycan bNAb epitope (SHIV.5MUT). Fourteen of 22 SHIV.5MUT-infected macaques developed potent bNAbs within one year of infection, in contrast to 0 of 14 macaques infected with the parental SHIV.BG505.N332. We isolated and characterized 12 distinct V3-glycan bNAb lineages from the animals with the greatest plasma breadth. Analysis of antibody-virus coevolution revealed shared routes of bNAb elicitation across animals, which enabled the design of novel priming and boosting immunogens. In parallel, we isolated 20 SARS-CoV-2 bNAb lineages from a convalescent, vaccinated patient. Five of these were pan-sarbecovirus bNAbs that neutralized all 18 viruses in our multiclade test panel. These bNAbs recognized the conserved class 1/4 or 5 epitopes on the Spike receptor binding domain (RBD). Prophylactic administration of one bNAb as either a recombinant protein or mRNA-LNP conferred protection against challenge with SARS-CoV-2 and a related bat virus with zoonotic potential. Overall, the immunogenetic, structural, and functional features of the HIV-1 and SARS-CoV-2 bNAbs identified here can inform next-generation vaccine design and can serve as templates for the next iteration of monoclonal antibody therapeutics to combat these viral pathogens
- Notes:
- Source: Dissertations Abstracts International, Volume: 87-12, Section: B.
- Advisors: Hahn, Beatrice H.; Locci, Michael Committee members: Luning Prak, Eline T.; Andrabi, Raiees A.; Stamatatos, Leonidas
- Ph.D. University of Pennsylvania 2026
- Vendor supplied data
- Local Notes:
- School code: 0175
- ISBN:
- 9798247972761
- Access Restriction:
- Restricted for use by site license
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