Comparative Efficacy of Inactivated and Live Attenuated Influenza Vaccines

Monto, Arnold S.; Ohmit, Suzanne E.; Petrie, Joshua G.; Johnson, Emileigh; Truscon, Rachel; Teich, Esther; Rotthoff, Judy R.; Boulton, Matthew L.; Victor, John C.

doi:10.1056/nejmoa0808652

Cited by 246 publications

(186 citation statements)

References 17 publications

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“…Although live attenuated vaccines (LAIVs) can induce of both humoral and cellular immunogenicity, in adults these vaccines have previously been associated with lower seroconversion rates and higher rates of laboratory-confirmed influenza when compared to trivalent influenza vaccine. These phenomena may possibly due to pre-existing immunogenicity at mucosal sites (7,29,30). Less than half of the vaccinees in a recent phase I clinical trial assessing safety and immunogenicity of a H7N9 LAIVs seroconverted (48%, (95% CI 29 4-67 5)) after one vaccination (31).…”

Section: Prime-boost Vaccinated Mice Intranasally Challenged With DIVmentioning

confidence: 99%

“…For the past 70 years vaccination has been the mainstay healthcare strategy against influenza infection (4)(5)(6). However traditional inactivated influenza vaccines (IIVs) confer strain-specific protection and do not typically induce the broad-spectrum immunity needed in the face of a newly emergent IAV (7)(8)(9). The possible threat of a pandemic outbreak has therefore catalysed the development of broadly protective IAV vaccines.…”

Section: Introductionmentioning

confidence: 99%

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Novel Bivalent Viral-Vectored Vaccines Induce Potent Humoral and Cellular Immune Responses Conferring Protection against Stringent Influenza A Virus Challenge

Chinnakannan

Mullarkey

Ulaszewska

et al. 2017

The Journal of Immunology

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Abstract:Seasonal influenza viruses (IAV) are a common cause of acute respiratory illness worldwide and generate a significant socio-economic burden. IAV rapidly mutate, necessitating annual vaccine reformulation as traditional vaccines do not typically induce broad-spectrum immunity. In addition to seasonal infections, emerging pandemic influenza viruses present a continued threat to global public health. Pandemic influenza viruses have consistently higher attack rates and are typically associated with greater mortality as compared to seasonal strains. Ongoing strategies to improve vaccine efficacy typically focus on providing broad-spectrum immunity, and while both B and T cells can mediate heterosubtypic responses, typical vaccine development will augment either humoral or cellular immunity. However, multipronged approaches, targeting several antigens, may limit the generation of viral escape mutants. There are few vaccine platforms that can deliver multiple antigens and generate robust cellular and humoral immunity. In this work, we describe a novel vaccination strategy, tested pre-clinically in mice, for the delivery of novel bivalent viral-vectored vaccines. Here, we show this strategy elicits potent T cell responses toward highly conserved internal antigens, whilst simultaneously inducing high levels of antibodies towards hemagglutinin (HA). Importantly, these humoral responses generate longlived plasma cells and generate antibodies capable of neutralising variant HA-expressing pseudotyped lentiviruses. Significantly, these novel viral-vectored vaccines induce strong immune responses capable of conferring protection in a stringent influenza A virus challenge.Thus, this vaccination regimen induces lasting efficacy toward influenza. Importantly, the simultaneous delivery of dual antigens may alleviate the selective pressure thought to potentiate antigenic diversity in avian influenza viruses.

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Section: Prime-boost Vaccinated Mice Intranasally Challenged With DIVmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel Bivalent Viral-Vectored Vaccines Induce Potent Humoral and Cellular Immune Responses Conferring Protection against Stringent Influenza A Virus Challenge

Chinnakannan

Mullarkey

Ulaszewska

et al. 2017

The Journal of Immunology

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“…Absolute efficacy in 18-49 year olds was lower than in children and efficacy was not demonstrated in the over 50s, leading to preferential recommendation for LAIV in children. 6,42 The common interpretation of this finding is that adults have prior immune history of influenza infections and possess cellular immunity to conserved internal viral proteins that can supress local mucosal replication of LAIV well enough to preclude a robust immune response. This cross-reactive immunity may be what protects many adults from severe illness during a pandemic.…”

Section: (Ii)prior Vaccination and Immunitymentioning

confidence: 99%

Urgent challenges in implementing live attenuated influenza vaccine

Singanayagam

Zambon

Lalvani

et al. 2018

The Lancet Infectious Diseases

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SummaryConflicting reports have emerged about the effectiveness of the live attenuated influenza vaccine (LAIV). LAIV appears to be protecting particularly poorly against currently circulating H1N1 viruses that are derived from the 2009 pandemic H1N1 (pH1N1) viruses. During the 2015/16 influenza season, when pH1N1 was the predominant virus, studies from the United States (US) reported a complete lack of effectiveness of LAIV in children. This led to a critical decision in the US to recommend that LAIV not be used in 2016/17 and to switch to the inactivated influenza vaccine. Other countries, including the UK, Canada and Finland, have continued to recommend use of LAIV. This policy divergence and uncertainty has far reaching implications for the entire global community, given the importance of LAIV production capability for pandemic preparedness. In this Personal View, we discuss possible explanations for the observed reduced effectiveness of LAIV and highlight underpinning scientific questions. Further research to understand the reasons for these observations is essential to enable informed public health policy and commercial decisions about vaccine production and development in coming years. 3 IntroductionInfluenza vaccination remains the main strategy to control the burden of seasonal influenza disease that affects 5-10% of adults and 20-30% of children, resulting in 250,000-500,000 deaths worldwide each year. 1,2 In the US, 140 million doses of vaccine are distributed each year and vaccination is estimated to prevent nearly a quarter of predicted influenza-associated deaths. 3 Vaccination is also the primary public health response to a global influenza pandemic.Influenza vaccines contain a mixture of three or four components designed to protect against the different viruses that circulate contemporaneously as seasonal influenza viruses. Currently, these are two influenza A viruses (H1N1 and H3N2 subtypes) and two influenza B viruses (Victoria and Yamagata lineages). Vaccine components are reviewed and updated regularly by the WHO in line with observed antigenic drift of influenza viruses.The traditional inactivated influenza vaccine (IIV) was introduced in the 1940s. IIV is administered by intramuscular/intradermal injection, is licensed for use in all ages and has a good safety record. However, effectiveness rates vary, averaging around 50-60%. 4,5 More recently, live attenuated influenza vaccine (LAIV) was demonstrated to have greater efficacy than IIV in children, with absolute efficacy rates of 75-80%. [6][7][8] Internal genes of LAIV viruses are derived from a cold-adapted, attenuated strain of virus, either Ann Arbor/1960 (from the US) or Leningrad/1957 (from Russia). Haemagglutinin (HA) and neuraminidase (NA) surface antigens are engineered to be representative of currently circulating strains. LAIV is nasally administered and vaccine viruses replicate only in the air-cooled environment of the human upper respiratory tract. This results in a mild and self-limiting infection; virus cannot replicate at t...

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“…4 Efficacy of inactivated influenza vaccine among adults has been demonstrated in several randomized placebo-controlled trials with the outcome of laboratory-confirmed influenza. [5][6][7][8][9][10][11][12] A recent meta-analysis reported a pooled vaccine efficacy of 59% (95% confidence interval, 51-67%) for the trivalent inactivated influenza vaccine among adults aged 18-64 years. 13 Among studies that enrolled participants with similar age distributions to those of pregnant women, demonstrated vaccine efficacy ranged from 54% to 89%.…”

mentioning

confidence: 99%

“…Over 3 influenza seasons, inactivated influenza vaccine efficacy ranged from 54% to 77%. [9][10][11] Although the efficacy and effectiveness of influenza vaccination in preventing influenza infection and illness has been demonstrated in nonpregnant, healthy adults, the immune response to vaccination might be different in pregnant women for several reasons. During pregnancy, immune alterations that allow the mother to tolerate fetal tissue of paternal origin occur.…”

mentioning

confidence: 99%