Association of vaccine handling conditions with effectiveness of live attenuated influenza vaccine against H1N1pdm09 viruses in the United States

Caspard, Hervé; Coelingh, Kathleen; Mallory, Raburn M.; Ambrose, Christopher S.

doi:10.1016/j.vaccine.2016.08.079

Cited by 36 publications

(24 citation statements)

References 31 publications

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“…Alternatively, low efficacy could be due to a vaccine's reduced ability to generate an immune response. There are many reasons why a vaccine might not be sufficiently immunogenic [23,24]: problems might have arisen with the strain contained in the vaccine during production [25], the age of the host (influenza vaccines result in lower immune responses in people over 65 years old [26,27]) or pre-existing immunity affecting the ability of the vaccine's immunogenicity [28]. The latter is called negative interference.…”

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confidence: 99%

Successes and failures of the live-attenuated influenza vaccine, can we do better?

Matrajt

Halloran

Antia

2018

Preprint

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Significance Statement:The live-attenuated influenza vaccine, in principle provides an important intervention for the control of both seasonal and pandemic influenza. However vaccine effectiveness studies have found seemingly contradictory results with effectiveness ranging from 0 to 50%. Based on mathematical models we suggest that a major factor responsible for the variable efficacy of the vaccine is negative interference -where pre-existing immunity precludes the vaccine from working. Our models suggest that there are broad regimes for which LAIV will fail to be immunogenic, but also allow us to make suggestions for the choice of vaccine strain that will allow optimization of protective immunity in different scenarios. AbstractLive-attenuated vaccines are usually highly effective against many acute viral infections. However, the effectiveness of the live attenuated influenza vaccine (LAIV) can vary widely, ranging from 0% effectiveness in some studies done in the United States to 50% in studies done in Europe. The reasons for these discrepancies remain largely unclear. In this paper we use mathematical models to explore how the efficacy of LAIV is affected by the degree of mismatch with the currently circulating influenza strain and interference with pre-existing immunity. The model incorporates two key antigenic distances -the distance between pre-existing immunity and the currently circulating strain as well as the LAIV strain. Our models show that a LAIV that is matched with the currently circulating strain is likely to have only modest efficacy. Our results suggest that the efficacy of the vaccine would be increased (optimized) if, rather than being matched to the circulating strain, it is antigenically slightly further from pre-existing immunity compared with the circulating strain. The models also suggest two regimes in which LAIV that is matched to circulating strains may provide effective protection. The first is in children before they have built immunity from circulating strains. The second is in response to novel strains (such as antigenic shifts) which are at substantial antigenic distance from previously circulating strains. Our models provide an explanation for the variation in vaccine effectiveness, both between children and adults as well as between studies of vaccine effectiveness observed during the 2014-15 influenza season in different countries.

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confidence: 99%

Successes and failures of the live-attenuated influenza vaccine, can we do better?

Matrajt

Halloran

Antia

2018

Preprint

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“…60 In response to this, vaccine manufacturers took the initiative to update the pH1N1 component of LAIV in their 2015/16 product to include the HA from a more recent pH1N1 isolate (A/Bolivia/559/2013) that contains a known HA stabilising mutation 55 . In addition, measures were taken to improve maintenance of the cold chain.…”

Section: (B)reduced Thermostability Of the Ph1n1 Componentmentioning

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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“…Suboptimal thermostability of the A(H1N1)pdm09 A/California/7/09 strain, linked to exposure to high environmental temperature, was proposed as one of the main explanations for the reduction in VE seen in 2013/2014 13. Based on these observations, the A/California/7/09 strain was replaced with the A/Bolivia/559/2013 strain on the premise that it was more heat stable.…”

Section: Possible Explanations For These Observationsmentioning

confidence: 99%

Live attenuated influenza vaccine (LAIV): recent effectiveness results from the USA and implications for LAIV programmes elsewhere

2017

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The USA has a long-standing paediatric influenza vaccination programme, including use of live attenuated influenza vaccine (LAIV). Following US evidence of apparent lack of vaccine effectiveness (VE) of LAIV in 2015/2016, particularly against A(H1N1)pdm09, the USA suspended the use of LAIV in the 2016/2017 season. The UK introduced LAIV for children in 2013/2014 and Finland in 2015/2016. Both countries have since been closely monitoring programme performance. In 2015/2016, the UK and Finland, unlike the USA, found evidence of significant VE of LAIV against laboratory-confirmed influenza. Several studies, however, reported relatively lower VE of LAIV against A(H1N1)pdm09 infection compared with inactivated influenza vaccine, although not for A(H3N2) or B. The reasons for these apparent differences remain under investigation. Both the UK and Finland continue to recommend the use of LAIV in children for the 2017/2018 season and are intensifying further monitoring of their childhood programmes against a range of end-points.

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Association of vaccine handling conditions with effectiveness of live attenuated influenza vaccine against H1N1pdm09 viruses in the United States

Abstract: NCT01997450.

Cited by 36 publications

References 31 publications

Successes and failures of the live-attenuated influenza vaccine, can we do better?

Successes and failures of the live-attenuated influenza vaccine, can we do better?

Urgent challenges in implementing live attenuated influenza vaccine

Live attenuated influenza vaccine (LAIV): recent effectiveness results from the USA and implications for LAIV programmes elsewhere

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