Next Article in Journal
Canonical and Non-Canonical Autophagy in HIV-1 Replication Cycle
Previous Article in Journal
Why Human Papillomaviruses Activate the DNA Damage Response (DDR) and How Cellular and Viral Replication Persists in the Presence of DDR Signaling
Article Menu
Issue 10 (October) cover image

Export Article

Open AccessArticle
Viruses 2017, 9(10), 269; doi:10.3390/v9100269

Live Attenuated Influenza Vaccine contains Substantial and Unexpected Amounts of Defective Viral Genomic RNA

Faculty of Health and Life Sciences, Coventry University, Science and Health Building, 20 Whitefriars Street Coventry CV1 2DS, UK
School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK
Authors to whom correspondence should be addressed.
Received: 21 August 2017 / Revised: 18 September 2017 / Accepted: 20 September 2017 / Published: 21 September 2017
(This article belongs to the Section Antivirals & Vaccines)
View Full-Text   |   Download PDF [749 KB, uploaded 22 September 2017]   |  


The live attenuated influenza vaccine FluMist® was withdrawn in the USA by the Centers for Disease Control and Prevention after its failure to provide adequate protective immunity during 2013–2016. The vaccine uses attenuated core type A and type B viruses, reconfigured each year to express the two major surface antigens of the currently circulating viruses. Here Fluenz™ Tetra, the European version of this vaccine, was examined directly for defective-interfering (DI) viral RNAs. DI RNAs are deleted versions of the infectious virus genome, and have powerful biological properties including attenuation of infection, reduction of infectious virus yield, and stimulation of some immune responses. Reverse transcription polymerase chain reaction followed by cloning and sequencing showed that Fluenz™ vaccine contains unexpected and substantial amounts of DI RNA arising from both its influenza A and influenza B components, with 87 different DI RNA sequences identified. Flu A DI RNAs from segment 3 replaced the majority of the genomic full-length segment 3, thus compromising its infectivity. DI RNAs arise during vaccine production and non-infectious DI virus replaces infectious virus pro rata so that fewer doses of the vaccine can be made. Instead the vaccine carries a large amount of non-infectious but biologically active DI virus. The presence of DI RNAs could significantly reduce the multiplication in the respiratory tract of the vaccine leading to reduced immunizing efficacy and could also stimulate the host antiviral responses, further depressing vaccine multiplication. The role of DI viruses in the performance of this and other vaccines requires further investigation. View Full-Text
Keywords: influenza A; influenza B; live attenuated vaccine; defective interfering RNA influenza A; influenza B; live attenuated vaccine; defective interfering RNA

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Gould, P.S.; Easton, A.J.; Dimmock, N.J. Live Attenuated Influenza Vaccine contains Substantial and Unexpected Amounts of Defective Viral Genomic RNA. Viruses 2017, 9, 269.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Viruses EISSN 1999-4915 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top