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Live, attenuated influenza virus (LAIV) vehicles are strong inducers of immunity toward influenza B virus.

ABSTRACT: Historically, vaccines developed toward influenza viruses of the B type using methodologies developed for influenza A viruses as a blueprint have not been equally efficacious or effective. Because most influenza research and public attention concerns influenza A viruses, these shortcomings have not been adequately addressed. In this manuscript, we utilized different influenza vaccine vehicles to compare immunogenicity and protection in mice and ferrets after vaccination against an influenza B virus. We report that plasmid DNA vaccines demonstrate low immunogenicity profiles and poor protection compared to either whole, inactivated influenza virus (IIV) or, live, attenuated influenza virus (LAIV) vaccines. When mixed prime:boost regimens using LAIV and IIV were studied, we observed a boosting effect in mice after priming with LAIV that was not seen when IIV was used as the prime. In ferrets LAIV induced high antibody titers after a single dose and provided a boost in IIV-primed animals. Regimens including LAIV as a prime demonstrated enhanced protection, and adjuvantation was required for efficacy using the IIV preparation. Our results differ from generally accepted influenza A virus vaccine models, and argue that strategies for control of influenza B virus should be considered separately from those for influenza A virus.

SUBMITTER: Huber VC

PROVIDER: S-EPMC2547490 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

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Live, attenuated influenza virus (LAIV) vehicles are strong inducers of immunity toward influenza B virus.

Huber Victor C VC Kleimeyer Loren H LH McCullers Jonathan A JA

Vaccine 20080815 42

Historically, vaccines developed toward influenza viruses of the B type using methodologies developed for influenza A viruses as a blueprint have not been equally efficacious or effective. Because most influenza research and public attention concerns influenza A viruses, these shortcomings have not been adequately addressed. In this manuscript, we utilized different influenza vaccine vehicles to compare immunogenicity and protection in mice and ferrets after vaccination against an influenza B vi ...[more]

PMID: 18708106

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Project description:LAIV and TIV are effective for prevention of influenza infection in children, but the mechanisms associated with protection are still not well defined. We analyzed the differences in B cell responses and transcriptional profiles. Compared to baseline, LAIV elicited a significant increase in naM-CM-/ve, memory and transitional B cells on day 30, while vaccination with TIV elicited an increase in number of plasmablasts on day 7. Antibody titers against the three vaccine strains (H1N1, H3N2 and B) were significantly higher in the TIV group and correlated with number of antibody-secreting cells. Regarding transcriptional profiles, both vaccines induced expression of interferon signaling, but at different time points, TIV on 1 day, and LAIV on day 7 day post-vaccination, the last only in children younger than 5 years old. Interferon-related genes over expressed in both vaccinated groups correlated with antibody titers of H3N2 vaccines strain. These results suggest that LAIV and TIV induced significant different B cell responses in vaccinated children. Early induction on interferon genes appears important for development of effective antibody responses. Longitudinal study with time points at baseline (day 0), 24hr, day 7 and day 30. 136 total samples analyzed. This was a prospective cohort of previously healthy children 6 months to 14 years of age enrolled between October 2011 and February 2012. Thirty seven subjects were randomized to receive one dose of either LAIV (FluMistM-BM-., MedImmune) (n= 20) or TIV (FluzoneM-BM-., Sanofi Pasteur) (n= 17). Two exceptions were applied to the randomization: four children with ages between 6 months and 2 years old received TIV, since LAIV is not licensed on this age group, and four children with controlled asthma also received TIV following CDCM-bM-^@M-^Ys recommendations. One child aged 6 months at the time of enrollment received two doses of the vaccine with one month interval apart, since it was his first influenza vaccination. Exclusion criteria included any medical comorbidities or chronic conditions (lung, kidney or heart disease), use of systemic steroids in the previous 2 weeks, and congenital or acquired immunodeficiencies. The 2011-2012 LAIV and TIV vaccines contained A/California/7/2009 (H1N1)-like, A/Perth/16/2009 (H3N2)-like and B/Brisbane/60/2008-like antigens, the same strains used on the 2010-2011 influenza vaccine. TIV recipients aged 6 to 35 months old received 0.25 mL intramuscularly and recipients aged 36 months and older received 0.5 mL. LAIV recipients received 0.2 mL by intranasal route, 0.1 mL per nostril. Blood samples were collected at four time points, on day zero prior to vaccination, and day 1, day 7 (range 6-8) and day 30 (range 27-33) post-vaccination.

Project description:Seasonal influenza epidemics and occasional pandemics threaten public health worldwide. New alternative strategies for generating recombinant viruses with vaccine potential are needed. Interestingly, influenza viruses circulating in different hosts have been found to have distinct codon usage patterns, which may reflect host adaptation. We therefore hypothesized that it is possible to make a human seasonal influenza virus that is specifically attenuated in human cells but not in eggs by converting its codon usage so that it is similar to that observed from avian influenza viruses. This approach might help to generate human live attenuated viruses without affecting their yield in eggs. To test this hypothesis, over 300 silent mutations were introduced into the genome of a seasonal H1N1 influenza virus. The resultant mutant was significantly attenuated in mammalian cells and mice, yet it grew well in embryonated eggs. A single dose of intranasal vaccination induced potent innate, humoral, and cellular immune responses, and the mutant could protect mice against homologous and heterologous viral challenges. The attenuated mutant could also be used as a vaccine master donor strain by introducing hemagglutinin and neuraminidase genes derived from other strains. Thus, our approach is a successful strategy to generate attenuated viruses for future application as vaccines.Vaccination has been one of the best protective measures in combating influenza virus infection. Current licensed influenza vaccines and their production have various limitations. Our virus attenuation strategy makes use of the codon usage biases of human and avian influenza viruses to generate a human-derived influenza virus that is attenuated in mammalian hosts. This method, however, does not affect virus replication in eggs. This makes the resultant mutants highly compatible with existing egg-based vaccine production pipelines. The viral proteins generated from the codon bias mutants are identical to the wild-type viral proteins. In addition, our massive genome-wide mutational approach further minimizes the concern over reverse mutations. The potential use of this kind of codon bias mutant as a master donor strain to generate other live attenuated viruses is also demonstrated. These findings put forward a promising live attenuated influenza vaccine generation strategy to control influenza.

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Live, attenuated influenza virus (LAIV) vehicles are strong inducers of immunity toward influenza B virus.

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Live, attenuated influenza virus (LAIV) vehicles are strong inducers of immunity toward influenza B virus.

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