Recombinant Vectors as Influenza Vaccines

Kopecky-Bromberg, Sarah A.; Palese, Peter

doi:10.1007/978-3-540-92165-3_13

Cited by 14 publications

(13 citation statements)

References 135 publications

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“…There has been interest in replicating viral vectors as candidates for HIV 2 or filovirus 3 vaccines, and adenoviruses have been noted as having particular benefits as potential recombinant-vector vaccines for influenza 4 and HIV 5 . Only a few replicating vector viruses, other than flavivirus chimeric recombinants between related flaviviruses, have advanced to phase 1 studies 6–10 .…”

Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity of an oral, replicating adenovirus serotype 4 vector vaccine for H5N1 influenza: a randomised, double-blind, placebo-controlled, phase 1 study

Gurwith

Lock

Taylor

et al. 2013

The Lancet Infectious Diseases

144

128

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SummaryBackgroundReplication-competent virus vector vaccines might have advantages compared with non-replicating vector vaccines. We tested the safety and immunogenicity of an oral adenovirus serotype 4 vector vaccine candidate (Ad4-H5-Vtn) expressing the haemagglutinin from an avian influenza A H5N1 virus.MethodsWe did this phase 1 study at four sites in the USA. We used a computer-generated randomisation list (block size eight, stratified by site) to assign healthy volunteers aged 18–40 years to receive one of five doses of Ad4-H5-Vtn (107 viral particles [VP], 108 VP, 109 VP, 1010 VP, 1011 VP) or placebo (3:1). Vaccine or placebo was given on three occasions, about 56 days apart. Participants, investigators, and study-site personnel were masked to assignment throughout the study. Subsequently, volunteers received a boost dose with 90 μg of an inactivated parenteral H5N1 vaccine. Primary immunogenicity endpoints were seroconversion by haemagglutination-inhibition (HAI), defined as a four-times rise compared with baseline titre, and HAI geometric mean titre (GMT). We solicited symptoms of reactogenicity daily for 7 days after each vaccination and recorded symptoms that persisted beyond 7 days as adverse events. Primary analysis was per protocol. This trial is registered with ClinicalTrials.gov, number NCT01006798.FindingsWe enrolled 166 participants (125 vaccine; 41 placebo) between Oct 19, 2009, and Sept 9, 2010. HAI responses were low: 13 of 123 vaccinees (11%, 95% CI 6–17) and three of 41 placebo recipients (7%, 2–20) seroconverted. HAI GMT was 6 (95% CI 5–7) for vaccinees, and 5 (5–6) for placebo recipients. However, when inactivated H5N1 vaccine became available, one H5N1 boost was offered to all participants. In this substudy, HAI seroconversion occurred in 19 of 19 participants in the 1011 VP cohort (100%; 95% CI 82–100) and eight of 22 placebo recipients (36%; 17–59); 17 of 19 participants in the 1011 VP cohort (89%; 67–99) achieved seroprotection compared with four of 22 placebo recipients (18%; 5–40); GMT was 135 (89–205) with 1011 VP, compared with 13 (7–21) with placebo. The cumulative frequency of abdominal pain, diarrhoea, and nasal congestion after all three vaccinations was significantly higher in vaccinees than placebo recipients (21 [16·8%] of 125 vs one [2·4%] of 41, p=0·017; 24 [19·2%] of 125 vs two [4·9%] of 41, p=0·027; 41 [32·8%] of 125 vs six [14·6%] of 41, p=0·028; respectively). No serious treatment-related adverse events occurred.InterpretationOral Ad4 vector priming might enhance the efficacy of poorly immunogenic vaccines such as H5N1.FundingWellcome Trust Foundation, PaxVax.

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Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity of an oral, replicating adenovirus serotype 4 vector vaccine for H5N1 influenza: a randomised, double-blind, placebo-controlled, phase 1 study

Gurwith

Lock

Taylor

et al. 2013

The Lancet Infectious Diseases

144

128

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“…A number of vector systems have been employed to express influenza HA and other influenza virus proteins in recombinant vaccine candidates for human seasonal as well as potentially pandemic avian influenza viruses. 61 Some recombinant systems could allow faster and safer development of master seed viruses and vaccine production in large volumes at lower cost and with greater speed than conventional TIV. On the other hand, the vectored approach faces the challenge of anti-vector immunity, which can dampen the response to repeat immunization.…”

Section: Live Attenuated Influenza Vaccinesmentioning

confidence: 99%

New technologies for influenza vaccines

Dormitzer

Tsai

Giudice

2012

Human Vaccines & Immunotherapeutics

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“…Adenoviruses (Ads) are nonenveloped DNA viruses originally identified as infectious agents responsible for certain acute respiratory infections. Ad infection usually manifests as mild disease, which is promptly resolved; however, infection of immunocompromised individuals can result in more severe disease (88,89). Several properties of Ad viruses are attractive for vaccine use, including relative ease of manipulation, infection of both dividing and nondividing cells, high levels of transgene expression, ability to grow to high titers in vitro and lack of integration in the host genome and stability (physical and genetic) (87,89,90).…”

Section: Adenovirusesmentioning

confidence: 99%

Novel Viral Vectored Vaccines for the Prevention of Influenza

Lambe

2012

Mol Med

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Influenza represents a substantial global healthcare burden, with annual epidemics resulting in 3-5 million cases of severe illness with a significant associated mortality. In addition, the risk of a virulent and lethal influenza pandemic has generated widespread and warranted concern. Currently licensed influenza vaccines are limited in their ability to induce efficacious and long-lasting herd immunity. In addition, and as evidenced by the H1N1 pandemic in 2009, there can be a significant delay between the emergence of a pandemic influenza and an effective, antibody-inducing vaccine. There is, therefore, a continued need for new, efficacious vaccines conferring cross-clade protection-obviating the need for biannual reformulation of seasonal influenza vaccines. Development of such a vaccine would yield enormous health benefits to society and also greatly reduce the associated global healthcare burden. There are a number of alternative influenza vaccine technologies being assessed both preclinically and clinically. In this review we discuss viral vectored vaccines, either recombinant live-attenuated or replication-deficient viruses, which are current lead candidates for inducing efficacious and long-lasting immunity toward influenza viruses. These alternate influenza vaccines offer real promise to deliver viable alternatives to currently deployed vaccines and more importantly may confer long-lasting and universal protection against influenza viral infection.

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Recombinant Vectors as Influenza Vaccines

Cited by 14 publications

References 135 publications

Safety and immunogenicity of an oral, replicating adenovirus serotype 4 vector vaccine for H5N1 influenza: a randomised, double-blind, placebo-controlled, phase 1 study

Safety and immunogenicity of an oral, replicating adenovirus serotype 4 vector vaccine for H5N1 influenza: a randomised, double-blind, placebo-controlled, phase 1 study

New technologies for influenza vaccines

Novel Viral Vectored Vaccines for the Prevention of Influenza

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