Comparisons of the Humoral and Cellular Immune Responses Induced by Live Attenuated Influenza Vaccine and Inactivated Influenza Vaccine in Adults

Hoft, Daniel F.; Lottenbach, Kathleen R.; Blazevic, Azra; Turan, Aldin; Blevins, Tamara P.; Pacatte, Thomas; Yu, Yinyi; Mitchell, Michelle C.; Hoft, Stella G.; Belshe, Robert B.

doi:10.1128/cvi.00414-16

Cited by 114 publications

(117 citation statements)

References 28 publications

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“…LAIV responses in young children are higher than in adults. For instance, LAIV when compared to inactivated vaccines induced smaller concentrations of antibodies in response to HA in adults (54). Previous findings have shown the benefit of taking a systems biology approach to assess gene expression responses to vaccinations (55, 56, 50).…”

Section: Discussionmentioning

confidence: 99%

Microarray Gene Expression Dataset Re-Analysis Reveals Variability in Influenza Infection and Vaccination

Rogers

Campos

Mias

2019

Preprint

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2Influenza, a communicable disease, affects thousands of people worldwide. Young children, 3 elderly, immunocompromised individuals and pregnant women are at higher risk for being 4 infected by the influenza virus. Our study aims to highlight differentially expressed genes in 5 influenza disease compared to influenza vaccination. We also investigate genetic variation 6 due to the age and sex of samples. To accomplish our goals, we conducted a meta-analysis 7 using publicly available microarray expression data. Our inclusion criteria included subjects with 8 influenza, subjects who received the influenza vaccine and healthy controls. We curated 18 9 microarray datasets for a total of 3,481 samples (1,277 controls, 297 influenza infection, 1,907 10 influenza vaccination). We pre-processed the raw microarray expression data in R using packages 11 available to pre-process Affymetrix and Illumina microarray platforms. We used a Box-Cox power 12 transformation of the data prior to our down-stream analysis to identify differentially expressed 13 genes. Statistical analyses were based on linear mixed effects model with all study factors and 14 successive likelihood ratio tests (LRT) to identify differentially-expressed genes. We filtered LRT 15 results by disease (Bonferroni adjusted p-value < 0.05) and used a two-tailed 10% quantile cutoff 16 to identify biologically significant genes. Furthermore, we assessed age and sex effects on the 17 disease genes by filtering for genes with a statistically significant (Bonferroni adjusted p-value < 18 0.05) interaction between disease and age, and disease and sex. We identified 4,889 statistically 19 significant genes when we filtered the LRT results by disease factor, and gene enrichment analysis 20 (gene ontology and pathways) included innate immune response, viral process, defense response 21 to virus, Hematopoietic cell lineage and NF-kappa B signaling pathway. Our quantile filtered gene 22 lists comprised of 978 genes each associated with influenza infection and vaccination. We also 23 identified 907 and 48 genes with statistically significant (Bonferroni adjusted p-value < 0.05) 24 disease-age and disease-sex interactions respectively. Our meta-analysis approach highlights 25 key gene signatures and their associated pathways for both influenza infection and vaccination. 26 1 Rogers LRK et al. Variability in Influenza Infection and VaccinationWe also were able to identify genes with an age and sex effect. This gives potential for improving 27 current vaccines and exploring genes that are expressed equally across ages when considering 28 universal vaccinations for influenza. 29 30

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Section: Discussionmentioning

confidence: 99%

Microarray Gene Expression Dataset Re-Analysis Reveals Variability in Influenza Infection and Vaccination

Rogers

Campos

Mias

2019

Preprint

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“…Because of these reasons one would expect that vaccination with LAIV would result in a broader immune response as compared to TIV and/or QIV. LAIV administration can indeed induce T cell responses [26,27] and a cross-reactive plasmablast response to heterovariant influenza strains that is greater than with IIV [28]. LAIV is also better for induction of influenza-specific IgA in the upper respiratory tract [27], which is considered one of the first lines of defence against influenza virus.…”

Section: Manuscriptmentioning

confidence: 99%

“…LAIV administration can indeed induce T cell responses [26,27] and a cross-reactive plasmablast response to heterovariant influenza strains that is greater than with IIV [28]. LAIV is also better for induction of influenza-specific IgA in the upper respiratory tract [27], which is considered one of the first lines of defence against influenza virus. However, vaccine-specific HI titers against homologous virus are sometimes lower after LAIV administration compared to IIV, and also induction of cross-reactive ADCC-antibodies in sera are not as good as with IIV, whereas natural and experimental infection do perform similarly [16,17].…”

Section: Manuscriptmentioning

confidence: 99%

Inactivated influenza virus vaccines: the future of TIV and QIV

Schotsaert

García‐Sastre

2017

Current Opinion in Virology

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Influenza viruses continue to be a major public health concern, despite the availability of vaccines. Currently licensed influenza vaccines aim at the induction of antibodies that target hemagglutinin, the major antigenic determinant on the surface of influenza virions that is responsible for attachment of the virus to the host cell that is to be infected. Currently licensed influenza vaccines come as inactivated or live attenuated influenza vaccines and are tri- or quadrivalent as they contain antigens of two influenza A and one or two influenza B strains that circulate in the human population, respectively. In this review we briefly compare trivalent and quadrivalent inactivated influenza vaccines (TIV and QIV) with live attenuated influenza vaccines (LAIV). The use of the latter vaccine type in children age 2 to 8 has been disrecommended recently by the American Centers for Disease Control and Prevention due to inferior vaccine effectiveness in this age group in recent seasons. This recommendation will favor the use of TIV and QIV over LAIV in the near future. However, there is much evidence from studies in humans that illustrate the benefit of LAIV and we discuss some of the mechanisms that contribute to broader protection against influenza viruses of different subtypes induced by natural infection and LAIV. The future challenge will be to apply these insights to allow induction of broader and long-lasting protection provided by TIV and QIV vaccines, e.g. by the use of adjuvants or combining LAIV with TIV and QIV. Other immune factors than serum hemagglutination inhibiting antibodies have shown to correlate with protection provided by TIV and QIV, which illustrates the need for other correlates of protection than hemagglutination inhibition by serum antibodies and justifies more focus on influenza antigens in the TIV and QIV other than hemagglutinin.

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“…Trivalent live attenuated influenza vaccine (LAIV) has previously been shown to provide broader protection against influenza A infection . LAIV mimics natural infection and both the innate and the adaptive immune responses are activated after LAIV …”

Section: Introductionmentioning

confidence: 99%

“…[2][3][4] LAIV mimics natural infection and both the innate and the adaptive immune responses are activated after LAIV. [5][6][7] The influenza virus has two major surface glycoproteins: the haemagglutinin (HA) and neuraminidase (NA), and antibodies directed towards both glycoproteins play an important role in protection against influenza virus. The haemagglutinin comprises an immunodominant head domain (composed of the majority of the HA1 subunit) and a stalk domain (mainly the HA2 subunit and the N-and C-terminal ends of HA1).…”

Section: Introductionmentioning

confidence: 99%

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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Comparisons of the Humoral and Cellular Immune Responses Induced by Live Attenuated Influenza Vaccine and Inactivated Influenza Vaccine in Adults

Cited by 114 publications

References 28 publications

Microarray Gene Expression Dataset Re-Analysis Reveals Variability in Influenza Infection and Vaccination

Microarray Gene Expression Dataset Re-Analysis Reveals Variability in Influenza Infection and Vaccination

Inactivated influenza virus vaccines: the future of TIV and QIV

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

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