Vaccines within vaccines: The use of adenovirus types 4 and 7 as influenza vaccine vectors

EricA Weaver

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Adenovirus Types 4 and 7 (Ad4 and Ad7) are associated with acute respiratory distress (ARD). In order to prevent widespread Ad-associated ARD (Ad-ARD) the United States military immunizes new recruits using a safe and effective lyophilized wildtype Ad4 and Ad7 delivered orally in an enteric-coated capsule. We cloned Ad4 and Ad7 and modified them to express either a GFP-Luciferase (GFPLuc) fusion gene or a centralized influenza H1 hemagglutinin (HA1-con). BALB/c mice were injected with GFPLuc expressing viruses muscularly (i.m.) and intranasally (i.n.). Ad4 induced significantly higher luciferase expression levels as compared with Ad7 by both routes. Ad7 transduction was restored using a human CD46+ transgenic mouse model. Mice immunized with serial dilutions of viruses expressing the HA1-con influenza vaccine gene were challenged with 100 MLD50 of influenza virus. Ad4 protected BALB/c mice at a lower dose by i.m. immunization as compared with Ad7. Unexpectedly, there was no difference in protection by i.n. immunization. Although Ad7 i.m. transduction was restored in CD46+ transgenic mice, protection against influenza challenge required even higher doses as compared with the BALB/c mice. However, Ad7 i.n. immunized CD46+ transgenic mice were better protected as compared with Ad4. Interestingly, the restoration of Ad7 transduction in CD46+ mice did not increase vaccine efficacy and indicates that Ad7 may transduce a different subset of cells through alternative receptors in the absence of CD46. These data indicate that both Ad4 and Ad7 can effectively induce anti-H1N1 immunity against a heterologous challenge using a centralized H1 gene. Future studies in non-human primates or human clinical trials will determine the overall effectiveness of Ad4 and Ad7 as vaccines for influenza.

Original languageEnglish (US)
Pages (from-to)544-556
Number of pages13
JournalHuman Vaccines and Immunotherapeutics
Volume10
Issue number3
DOIs
StatePublished - 2014

Fingerprint

Influenza Vaccines
Adenoviridae
Vaccines
Luciferases
Transgenic Mice
Human Influenza
Immunization
Viruses
Gene Fusion
Hemagglutinins
Orthomyxoviridae
Primates
Genes
Capsules
Immunity
Clinical Trials

Keywords

  • Adenovirus
  • Adenovirus type 4
  • Adenovirus type 7
  • Centralized gene
  • Hemagglutinin
  • Influenza
  • Vaccine
  • Viral vector

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

Vaccines within vaccines : The use of adenovirus types 4 and 7 as influenza vaccine vectors. / Weaver, EricA.

In: Human Vaccines and Immunotherapeutics, Vol. 10, No. 3, 2014, p. 544-556.

Research output: Contribution to journalArticle

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