Live Attenuated Influenza Vaccine in Children Induces B-Cell Responses in Tonsils

Mohn, Kristin Greve-Isdahl; Brokstad, Karl Albert; Pathirana, Rishi D.; Bredholt, Geir; Jul-Larsen, Åsne; Trieu, Mai-Chi; Lartey, Sarah; Montemoli, Emanuele; Tøndel, Camilla; Aarstad, Hans Jørgen; Cox, Rebecca Jane

doi:10.1093/infdis/jiw230

Cited by 41 publications

(40 citation statements)

References 34 publications

(43 reference statements)

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“…Here, we aimed to further understand the T cell response in children using optimized libraries of CD4 and CD8 peptides representing unique T cell epitopes from the H1N1pdm09 virus. In the children, we found that only H1N1pdm09‐specific CD4 responses were boosted after LAIV and no change in CD8 responses was observed …”

Section: Discussionmentioning

confidence: 80%

“…The LAIV vaccine is intended to mimic a natural infection and stimulate the local immune response. We have in a previous study, shown that LAIV induces local influenza‐specific IgA production . As there are some degree of compartmentalization of the immune system, we cannot expect to observe the same degree of immune response systemically as with parenteral administered vaccines.…”

Section: Discussionmentioning

confidence: 87%

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Functional immune response to influenza H1N1 in children and adults after live attenuated influenza virus vaccination

et al. 2019

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Influenza virus is a major respiratory pathogen, and vaccination is the main method of prophylaxis. In 2012, the trivalent live attenuated influenza vaccine (LAIV) was licensed in Europe for use in children. Vaccine‐induced antibodies directed against the main viral surface glycoproteins, haemagglutinin (HA) and neuraminidase (NA) play important roles in limiting virus infection. The objective of this study was to dissect the influenza‐specific antibody responses in children and adults, and T cell responses in children induced after LAIV immunization to the A/H1N1 virus. Blood samples were collected pre‐ and at 28 and 56 days post‐vaccination from 20 children and 20 adults. No increase in micro‐neutralization (MN) antibodies against A/H1N1 was observed after vaccination. A/H1N1 stalk‐specific neutralizing and NA‐inhibiting (NI) antibodies were boosted in children after LAIV. Interferon γ‐producing T cells increased significantly in children, and antibody‐dependent cellular‐mediated cytotoxic (ADCC) cell activity increased slightly in children after vaccination, although this change was not significant. The results indicate that the NI assay is more sensitive to qualitative changes in serum antibodies after LAIV. There was a considerable difference in the immune response in children and adults after vaccination, which may be related to priming and previous influenza history. Our findings warrant further studies for evaluating LAIV vaccination immunogenicity.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 87%

Functional immune response to influenza H1N1 in children and adults after live attenuated influenza virus vaccination

et al. 2019

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“…LAIV have been engineered by reverse genetics using the HA and NA genes from circulating viruses and an attenuated, temperature-sensitive, cold-adapted backbone, which prevents replication of the virus at temperatures above 33°C, thus limiting virus infection to the upper airways (8,9). Following inhalation of LAIV, the palatine tonsils, the NALT equivalent in humans, is the site where the humoral immune response is initiated (15). Although the vaccine is clearly able to elicit HA-specific neutralizing antibodies, it is still unclear whether protective influenza-specific T cells are generated in humans following LAIV vaccination (16,17).…”

Section: Discussionmentioning

confidence: 99%

Nasal-associated lymphoid tissues (NALTs) support the recall but not priming of influenza virus-specific cytotoxic T cells

Pizzolla

Wang

Groom

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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The lymphoid tissue that drains the upper respiratory tract represents an important induction site for cytotoxic T lymphocyte (CTL) immunity to airborne pathogens and intranasal vaccines. Here, we investigated the role of the nasal-associated lymphoid tissues (NALTs), which are mucosal-associated lymphoid organs embedded in the submucosa of the nasal passage, in the initial priming and recall expansion of CD8+ T cells following an upper respiratory tract infection with a pathogenic influenza virus and immunization with a live attenuated influenza virus vaccine. Whereas NALTs served as the induction site for the recall expansion of memory CD8+ T cells following influenza virus infection or vaccination, they failed to support activation of naïve CD8+ T cells. Strikingly, NALTs, unlike other lymphoid tissues, were not routinely surveyed during the steady state by circulating T cells. The selective recruitment of memory T cells into these lymphoid structures occurred in response to infection-induced elevation of the chemokine CXCL10, which attracted CXCR3+ memory CD8+ T cells. These results have significant implications for intranasal vaccines, which deliver antigen to mucosal-associated lymphoid tissue and aim to elicit protective CTL-mediated immunity.

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“…The lack of a clear correlate of protection for LAIV impairs our understanding of immunogenicity; however, a Norwegian study demonstrated that children vaccinated with LAIV had significant haemagglutination inhibition titre and salivary IgA against H3N2 and B viruses but not for pH1N1. 11 The extent of attenuation in internal viral genes could be key to take rate in different age groups. In Russia, a more attenuated viral strain (47x passaged Leningrad/1957) was developed for use in children, where as a lower passage variant is used in adults.…”

Section: (Iii)biological Characteristics Of the Ph1n1 Virus (A)reducementioning

confidence: 99%

“…Yet, the immune response stimulated is robust and unlike IIV includes cellular, humoral and mucosal responses. [9][10][11] The "Leningrad" LAIV has been used widely in Russia for over 50 years. 12 The "Ann Arbor" product became licensed in the US in 2003 and is available for 2-49 year olds, in Canada since 2010 for 2-59 year olds, and in the European Union since 2011 for 2-17 year olds.…”

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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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Live Attenuated Influenza Vaccine in Children Induces B-Cell Responses in Tonsils

Cited by 41 publications

References 34 publications

Functional immune response to influenza H1N1 in children and adults after live attenuated influenza virus vaccination

Functional immune response to influenza H1N1 in children and adults after live attenuated influenza virus vaccination

Nasal-associated lymphoid tissues (NALTs) support the recall but not priming of influenza virus-specific cytotoxic T cells

Urgent challenges in implementing live attenuated influenza vaccine

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