Article

Quadrivalent Ann Arbor strain live-attenuated influenza vaccine

MedImmune, LLC, Gaithersburg, MD, USA.
Expert Review of Vaccines (Impact Factor: 4.21). 11/2012; 11(11). DOI: 10.1586/erv.12.108
Source: PubMed
ABSTRACT
Influenza B is responsible for significant morbidity in children and adults worldwide. For more than 25 years, two antigenically distinct lineages of influenza B viruses, B/Yamagata and B/Victoria, have cocirculated globally. Current influenza vaccine formulations are trivalent and contain two influenza subtype A strains (A/H1N1 and A/H3N2) but only one B strain. In a half of recent influenza seasons, the predominant circulating influenza B lineage was different from that contained in trivalent influenza vaccines. A quadrivalent live attenuated influenza vaccine (Q/LAIV) that contains two B strains, one from each lineage, has been developed to help provide broad protection against influenza B. Q/LAIV was recently approved for use in the USA in eligible individuals 2-49 years of age. This review summarizes clinical trial data in support of Q/LAIV.

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10.1586/ERV.12.108
1293
ISSN 1476-0584
www.expert-reviews.com
Vaccine Prole
© 2012 Expert Reviews Ltd
Since the 1970s, seasonal influenza vaccines have
been trivalent, composed of two influenza A
strains (A/H1N1 and A/H3N2) and one type
B strain [1] . The viral strains included in the vac-
cine are chosen annually by the WHO [101] and
national authorities based on ongoing influenza
epidemiology and surveillance. Since 1985, two
antigenically distinct lineages of influenza B
viruses have circulated globally (Yamagata and
Victoria) [2], but only one B strain from one
lineage is chosen for inclusion in trivalent vac-
cines. Owing to antigenic divergence, limited
immunologic cross-reactivity exists between
the B lineages such that immunization against
one lineage does not provide optimal protection
against the heterologous lineage [3, 102]. Vaccine-
induced protection against influenza B has
been suboptimal owing to frequent mismatch
between circulating and immunizing B line-
ages, with mismatches occurring in five out of
ten influenza seasons in the USA from 2001 to
2011 and four out of eight influenza seasons in
the EU from 2003 to 2011 (Figure 1) [4] .
Influenza B is responsible for significant
morbidity in children and adults worldwide.
According to surveillance data from the USA and
Europe, from 2001–2002 through 2010–2011
(excluding the 2009–2010 pandemic), on
average 24 and 23% of influenza samples, respec-
tively, were positive for influenza B [4]. Influenza
B causes disease in all age groups, but older
children and young adults tend to have higher
rates of influenza B illness relative to influenza
A [5,6]. Medically attended illnesses due to influ-
enza A and B are generally similar with regard to
symptoms, severity and rates of influenza-related
complications [7–19] . Studies of severe influenza
disease have demonstrated that influenza B
infections also cause a significant proportion of
influenza-attributable hospitalizations [20,21] .
Vaccination is considered the best strategy for
reducing influenza illness [22]. However, reduced
efficacy resulting from mismatch between the
lineage of the B strain included in trivalent
influenza vaccines and that of the predominant
circulating strain has resulted in suboptimal pro-
tection in recent years. Including influenza B
viruses of both lineages in an annual formulation
of seasonal influenza vaccines would eliminate
potential lineage-level mismatch between immu-
nizing and circulating B viruses and improve
protection against influenza B. A recent analysis
by the US CDC projected that between 2001
and 2009, the benefit of all trivalent vaccines
being replaced by quadrivalent influenza vac-
cines would have been 2.74 million fewer cases
Seth L Toback
1
, Myron
J Levin
2
, Stan L Block
3
,
Robert B Belshe
4
,
Christopher S
Ambrose*
1
and
Judith Falloon
1
1
MedImmune, LLC, Gaithersburg,
MD, USA
2
University of Colorado Denver School
of Medicine, Aurora, CO, USA
3
Kentucky Pediatric and Adult Research,
Bardstown, KY, USA
4
Saint Louis University School of
Medicine, Saint Louis, MO, USA
*Author for correspondence:
Tel.: +1 301 398 4454
Fax: +1 301 398 9454
ambrosec@medimmune.com
Influenza B is responsible for significant morbidity in children and adults worldwide. For more
than 25 years, two antigenically distinct lineages of influenza B viruses, B/Yamagata and
B/Victoria, have cocirculated globally. Current influenza vaccine formulations are trivalent and
contain two influenza subtype A strains (A/H1N1 and A/H3N2) but only one B strain. In a half
of recent influenza seasons, the predominant circulating influenza B lineage was different from
that contained in trivalent influenza vaccines. A quadrivalent live-attenuated influenza vaccine
(Q/LAIV) that contains two B strains, one from each lineage, has been developed to help provide
broad protection against influenza B. Q/LAIV was recently approved for use in the USA in eligible
individuals 2–49 years of age. This review summarizes clinical trial data in support of Q/LAIV.
Quadrivalent Ann Arbor strain
live-attenuated influenza
vaccine
Expert Rev. Vaccines 11(11), 1293–1303 (2012)
Expert Review Vaccines
© 2012 Expert Reviews Ltd
10.1586/ERV.12.108
1476-0584
1744-8395
Vaccine Profile
Keywords: adults • children • clinical trials • immunogenicity • inuenza B • intranasal • quadrivalent live-attenuated
inuenza vaccine • safety
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Expert Rev. Vaccines 11(11), (2012)
1294
Vaccine Prole
of influenza illnesses and 21,440 fewer hospitalizations in the
USA [23].
Overview of available influenza vaccines
Influenza vaccines in current use fall into two categories: trivalent
inactivated influenza vaccines (TIVs) and trivalent live-attenuated
influenza vaccines (LAIVs).
Trivalent inactivated vaccines
The majority of currently approved seasonal (nonpandemic) influ-
enza vaccines are TIVs of one of the following two formulations:
split-virion vaccines, which are derived by disrupting whole virus
preparations, and subunit vaccines, which typically enrich for
the surface antigens hemagglutinin (HA) and neuraminidase,
although the only standardized component is HA. Beyond this
difference, TIVs differ by whether or not they include an adjuvant
or a preservative, the substrate in which the antigens are produced,
the dose of antigen included and the route of administration.
Because split-virion and subunit TIVs are generally only modestly
immunogenic, some vaccine preparations incorporate adjuvants
to increase immunogenicity [24]. Most influenza vaccines are pro-
duced in chicken eggs; however, several seasonal inactivated influ-
enza vaccines manufactured using cell culture are approved for
use in the EU. A high-dose TIV that uses 60 µg of HA per strain
per dose was recently approved for use in individuals 65 years
of age in the USA [1] . The majority of TIVs are administered as
Figure 1. The percentage of circulating influenza B strains that were a lineage match (homologous lineage) or mismatch
(heterologous lineage) with the B lineage included in the influenza vaccines by influenza season between 2001 and 2011 in
the USA and Europe. Lineage match/mismatch (A) in the USA and (B) in Europe. The B lineage contained in the vaccine is indicated
below each season.
Adapted with permission from
[4].
2001–
2002
Yamagata
0
20
40
60
80
100
0
20
40
60
80
100
2002–
2003
Victoria
2003–
2004
Victoria
2004–
2005
Yamagata
2005–
2006
Yamagata
Influenza season and vaccine lineage
2008–
2009
Yamagata
2006–
2007
Victoria
2007–
2008
Victoria
2009–
2010
Victoria
2010
2011
Victoria
2001–
2002
Yamagata
2002–
2003
Victoria
Data not
available
23
77
93
26
81
23
98
83
16
6
100
7
74
19
77
17
84
94
20
80
56
9
91
99
1
3
97
94
92
8
6
56
44
44
2003–
2004
Victoria
2004–
2005
Yamagata
2005–
2006
Yamagata
Influenza season and vaccine lineage
Influenza B
strains by lineage (%)
Influenza B
strains by lineage (%)
Homologous-lineage influenza B Heterologous-lineage influenza B
2008–
2009
Yamagata
2006–
2007
Victoria
2007–
2008
Victoria
2009–
2010
Victoria
2010
2011
Victoria
A
B
2
Toback, Levin, Block, Belshe, Ambrose & Falloon
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    • "To address this problem, WHO suggested in 2012 the addition of influenza B virus strains of both lineages in the next season's influenza vaccine, thus turning the conventional trivalent vaccine into a quadrivalent vaccine [10]. The immunogenicity and the lack of meaningful immune interference between virus strains in quadrivalent vaccine were proven in adults and in children [2]. "
    [Show abstract] [Hide abstract] ABSTRACT: Introduction At present, two phylogenetically distinct influenza B virus lineages, B/Yamagata and B/Victoria, co-circulate worldwide and can cause significant morbidity and mortality. Objective The aim of this study was to determine the prevalences of two influenza B virus lineages in the population of Vojvodina and to identify their antigenic and phylogenetic properties. Methods A total of 369 and 334 nasopharyngeal, or nasal/throat swab samples, collected during the 2012/2013 and 2013/2014 seasons, respectively, were tested using specific singleplex influenza A, influenza B, influenza B/Yamagata and influenza B/Victoria real-time reverse transcription polymerase chain reaction (RT-PCR) assays. Antigenic and genetic testing were done by hemagglutination inhibition assay and hemagglutinin and neuraminidase gene sequence analysis, respectively. Results During the 2012/2013 season, influenza B viruses were present in 53.4% (101/189) of influenza positive samples.The B/Yamagata-like viruses (81.2%) significantly predominated over the B/Victoria-like viruses (18.8%). Comparing to B/Victoria-like positive patients, among B/Yamagata-like positive patients, children 5-14 years of age were significantly more represented (5.3% vs. 35.4%, respectively), as well as patients with mild form of illness (15.8% vs. 45.1%, respectively). The results of sequence analysis and antigenic testing showed that tested viruses were not closely related to B/Wisconsin/1/2010, the vaccine virus for 2012/2013. During the 2013/2014 season influenza B viruses were not detected. Conclusion The results of this study confirmed the health significance of influenza B viruses and indicated that B/Yamagata-like viruses were significantly more prevalent than B/Victoria lineage viruses, during the 2012/2013 season.They also showed a sub-optimal match between the tested viruses and the vaccine virus for season 2012/2013.
    Full-text · Article · Jul 2015 · Srpski arhiv za celokupno lekarstvo
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    • "For influenza B viruses, antigenic relatedness is further complicated by the existence of the two distinct lineages. Recent surveillance data from the United States and Europe between 2001 and 2011 showed that 46–58% of circulating influenza B lineages were mismatched to the vaccine strain [6,7]. Although Shanghai has the highest GDP in China, the coverage rate of influenza vaccination is low, largely because of the limited public knowledge about influenza and vaccine-related benefits and the annual influenza vaccination having no government reimbursement [8]. "
    [Show abstract] [Hide abstract] ABSTRACT: A new quadrivalent influenza vaccine has been available for influenza B, which can pose a significant global health burden. Shanghai has the highest GDP and largest metropolitan population in China. To understand the impact of influenza B in Shanghai in terms of age-related incidence and relative prevalence compared with other subtypes, we conducted this retrospective epidemiological study of influenza B in the 2009-2014 seasons. A total of 71 354 outpatients with influenza-like illness were included, and both lineages of influenza B and subtypes of influenza A were identified using real-time RT-PCR. The antigenic characteristics of influenza B isolates were analysed by sequencing and reciprocal haemagglutinin inhibition assay. On average, 33.45% of influenza strains were influenza B, and 40.20% of strains isolated from children were influenza B. The incidence of influenza B was highest (12.52 per 100 people with influenza-like illness) in children ages 6-17 years and usually peaked in this age group at the early stage of an influenza B epidemic. Overall, both matched and mismatched influenza B strains co-circulated in Shanghai annually, and 44.57% of the circulating influenza B belonged to the opposite lineage of the vaccine strains. We concluded that influenza B has caused a substantial impact in Shanghai and that school-aged children play a key role in the transmission of influenza B. Hence, it may be beneficial to prioritize influenza vaccination for school-aged children to mitigate the outbreaks of influenza B. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Apr 2015 · Clinical Microbiology and Infection
    • "tains the live, weakened Ann Arbor influenza strain. This weakened version can replicate efficiently only in limited conditions (Toback et al., 2012). The U.S. FDA (2012a) ap proved it in 2012 for administration to healthy children at least age 2 through adults up to age 49. "
    [Show abstract] [Hide abstract] ABSTRACT: The best way to prevent influenza and its potentially life-threatening complications is by receiving the annual flu immunization at the earliest opportunity. As patient educators, nurses should help individuals, families, and the community receive the benefits of this important illness prevention strategy.
    No preview · Article · Jul 2014 · Medsurg nursing: official journal of the Academy of Medical-Surgical Nurses
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