Optimization of Prime-Boost Vaccination Strategies Against Mouse-Adapted Ebolavirus in a Short-Term Protection Study

Jenna Aviles, Alexander Bello, Gary Wong, Hugues Fausther-Bovendo, Xiangguo Qiu, Gary Kobinger

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

In nonhuman primates, complete protection against an Ebola virus (EBOV) challenge has previously been achieved after a single injection with several vaccine platforms. However, long-term protection against EBOV after a single immunization has not been demonstrated to this date. Interestingly, prime-boost regimens have demonstrated longer protection against EBOV challenge, compared with single immunizations. Since prime-boost regimens have the potential to achieve long-term protection, determining optimal vector combinations is crucial. However, testing prime-boost efficiency in long-term protection studies is time consuming and resource demanding. Here, we investigated the optimal prime-boost combination, using DNA, porcine-derived adeno-associated virus serotype 6 (AAV-po6), and human adenovirus serotype 5 (Ad5) vector, in a short-term protection study in the mouse model of EBOV infection. In addition, we also investigated which immune parameters were indicative of a strong boost. Each vaccine platform was titrated in mice to identify which dose (single immunization) induced approximately 20% protection after challenge with a mouse-adapted EBOV. These doses were then used to determine the protection efficacy of various prime-boost combinations, using the same mouse model. In addition, humoral and cellular immune responses against EBOV glycoprotein were analyzed by an enzyme-linked immunosorbent assay, a neutralizing antibody assay, and an interferon γ-specific enzyme-linked immunospot assay. When DNA was used as a prime, Ad5 boost induced the best protection, which correlated with a higher cellular response. In contrast, when AAV-po6 or Ad5 were injected first, better protection was achieved after DNA boost, and this correlated with a higher total glycoprotein-specific immunoglobulin G titer. Prime-boost regimens using independent vaccine platforms may provide a useful strategy to induce long-term immune protection against filoviruses.

Original languageEnglish (US)
Pages (from-to)S389-S397
JournalJournal of Infectious Diseases
Volume212
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Keywords

  • adeno-associated virus
  • adenovirus
  • DNA
  • Ebola virus
  • prime-boost
  • vaccine

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Optimization of Prime-Boost Vaccination Strategies Against Mouse-Adapted Ebolavirus in a Short-Term Protection Study'. Together they form a unique fingerprint.

Cite this