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Systems biology of vaccination for seasonal influenza in humans.

Nakaya HI, Wrammert J, Lee EK, Racioppi L, Marie-Kunze S, Haining WN, Means AR, Kasturi SP, Khan N, Li GM, McCausland M, Kanchan V, Kokko KE, Li S, Elbein R, Mehta AK, Aderem A, Subbarao K, Ahmed R, Pulendran B - Nat. Immunol. (2011)

Bottom Line: Here we have used a systems biology approach to study innate and adaptive responses to vaccination against influenza in humans during three consecutive influenza seasons.We studied healthy adults vaccinated with trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV).Thus, systems approaches can be used to predict immunogenicity and provide new mechanistic insights about vaccines.

View Article: PubMed Central - PubMed

Affiliation: Emory Vaccine Center, Emory University, Atlanta, Georgia, USA.

ABSTRACT
Here we have used a systems biology approach to study innate and adaptive responses to vaccination against influenza in humans during three consecutive influenza seasons. We studied healthy adults vaccinated with trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV). TIV induced higher antibody titers and more plasmablasts than LAIV did. In subjects vaccinated with TIV, early molecular signatures correlated with and could be used to accurately predict later antibody titers in two independent trials. Notably, expression of the kinase CaMKIV at day 3 was inversely correlated with later antibody titers. Vaccination of CaMKIV-deficient mice with TIV induced enhanced antigen-specific antibody titers, which demonstrated an unappreciated role for CaMKIV in the regulation of antibody responses. Thus, systems approaches can be used to predict immunogenicity and provide new mechanistic insights about vaccines.

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Molecular signature induced by LAIV vaccination. (a) Interferon (IFN)-related genes differentially expressed after LAIV vaccination. Solid and dashed lines represent respectively, direct and indirect interactions reported for the genes. The colors represent the mean fold-change in gene expression on days 3 or 7 compared to day 0 in all LAIV vaccinees. Genes with expression fold-change highest at day 3 or day 7 post-vaccination are shown on the left or on the right of the network, respectively. (b) Induction of key IFN-related genes was confirmed by quantitative RT-PCR. PBMCs of healthy subjects were stimulated in vitro with different vaccines for 24h. The GAPDH-normalized expression levels of OAS1, IRF7, Mx2 and STAT1 in stimulated PBMCs were compared to those of PBMCs non-stimulated.
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Figure 2: Molecular signature induced by LAIV vaccination. (a) Interferon (IFN)-related genes differentially expressed after LAIV vaccination. Solid and dashed lines represent respectively, direct and indirect interactions reported for the genes. The colors represent the mean fold-change in gene expression on days 3 or 7 compared to day 0 in all LAIV vaccinees. Genes with expression fold-change highest at day 3 or day 7 post-vaccination are shown on the left or on the right of the network, respectively. (b) Induction of key IFN-related genes was confirmed by quantitative RT-PCR. PBMCs of healthy subjects were stimulated in vitro with different vaccines for 24h. The GAPDH-normalized expression levels of OAS1, IRF7, Mx2 and STAT1 in stimulated PBMCs were compared to those of PBMCs non-stimulated.

Mentions: The transcriptome analysis of vaccinees revealed that LAIV and TIV vaccines induce quite different gene signatures (Supplementary Fig. 3a). However the expression of 1,445 probe sets was similarly altered by both vaccines (Supplementary Fig. 3a). Among these common differentially expressed genes (DEG), Ingenuity Pathway Analysis identified a network comprised of several genes related to inflammatory and antimicrobial responses (Supplementary Fig. 3b). These indicated that processes related to innate immunity may influence the immunogenicity of each vaccine. The complete list of DEGs after TIV and LAIV vaccination is shown in Supplementary Table 1. The expression of several interferon (IFN) related genes was altered after LAIV but not TIV vaccination (Fig. 2a,b). Type 1 interferons are central components of the innate immune response to virus16. Therefore the increased expression of type I IFN-related genes may be attributed to the replication competence of the LAIV vaccine. Our analysis identified genes highly associated with the IFN signaling pathways, such as STAT1, STAT2, TLR7, IRF3 and IRF7 (Fig. 2a). It is important to note that the fold-change difference of many IFN-related genes was highest at day 3 post-LAIV immunization (Fig. 2a).


Systems biology of vaccination for seasonal influenza in humans.

Nakaya HI, Wrammert J, Lee EK, Racioppi L, Marie-Kunze S, Haining WN, Means AR, Kasturi SP, Khan N, Li GM, McCausland M, Kanchan V, Kokko KE, Li S, Elbein R, Mehta AK, Aderem A, Subbarao K, Ahmed R, Pulendran B - Nat. Immunol. (2011)

Molecular signature induced by LAIV vaccination. (a) Interferon (IFN)-related genes differentially expressed after LAIV vaccination. Solid and dashed lines represent respectively, direct and indirect interactions reported for the genes. The colors represent the mean fold-change in gene expression on days 3 or 7 compared to day 0 in all LAIV vaccinees. Genes with expression fold-change highest at day 3 or day 7 post-vaccination are shown on the left or on the right of the network, respectively. (b) Induction of key IFN-related genes was confirmed by quantitative RT-PCR. PBMCs of healthy subjects were stimulated in vitro with different vaccines for 24h. The GAPDH-normalized expression levels of OAS1, IRF7, Mx2 and STAT1 in stimulated PBMCs were compared to those of PBMCs non-stimulated.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3140559&req=5

Figure 2: Molecular signature induced by LAIV vaccination. (a) Interferon (IFN)-related genes differentially expressed after LAIV vaccination. Solid and dashed lines represent respectively, direct and indirect interactions reported for the genes. The colors represent the mean fold-change in gene expression on days 3 or 7 compared to day 0 in all LAIV vaccinees. Genes with expression fold-change highest at day 3 or day 7 post-vaccination are shown on the left or on the right of the network, respectively. (b) Induction of key IFN-related genes was confirmed by quantitative RT-PCR. PBMCs of healthy subjects were stimulated in vitro with different vaccines for 24h. The GAPDH-normalized expression levels of OAS1, IRF7, Mx2 and STAT1 in stimulated PBMCs were compared to those of PBMCs non-stimulated.
Mentions: The transcriptome analysis of vaccinees revealed that LAIV and TIV vaccines induce quite different gene signatures (Supplementary Fig. 3a). However the expression of 1,445 probe sets was similarly altered by both vaccines (Supplementary Fig. 3a). Among these common differentially expressed genes (DEG), Ingenuity Pathway Analysis identified a network comprised of several genes related to inflammatory and antimicrobial responses (Supplementary Fig. 3b). These indicated that processes related to innate immunity may influence the immunogenicity of each vaccine. The complete list of DEGs after TIV and LAIV vaccination is shown in Supplementary Table 1. The expression of several interferon (IFN) related genes was altered after LAIV but not TIV vaccination (Fig. 2a,b). Type 1 interferons are central components of the innate immune response to virus16. Therefore the increased expression of type I IFN-related genes may be attributed to the replication competence of the LAIV vaccine. Our analysis identified genes highly associated with the IFN signaling pathways, such as STAT1, STAT2, TLR7, IRF3 and IRF7 (Fig. 2a). It is important to note that the fold-change difference of many IFN-related genes was highest at day 3 post-LAIV immunization (Fig. 2a).

Bottom Line: Here we have used a systems biology approach to study innate and adaptive responses to vaccination against influenza in humans during three consecutive influenza seasons.We studied healthy adults vaccinated with trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV).Thus, systems approaches can be used to predict immunogenicity and provide new mechanistic insights about vaccines.

View Article: PubMed Central - PubMed

Affiliation: Emory Vaccine Center, Emory University, Atlanta, Georgia, USA.

ABSTRACT
Here we have used a systems biology approach to study innate and adaptive responses to vaccination against influenza in humans during three consecutive influenza seasons. We studied healthy adults vaccinated with trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV). TIV induced higher antibody titers and more plasmablasts than LAIV did. In subjects vaccinated with TIV, early molecular signatures correlated with and could be used to accurately predict later antibody titers in two independent trials. Notably, expression of the kinase CaMKIV at day 3 was inversely correlated with later antibody titers. Vaccination of CaMKIV-deficient mice with TIV induced enhanced antigen-specific antibody titers, which demonstrated an unappreciated role for CaMKIV in the regulation of antibody responses. Thus, systems approaches can be used to predict immunogenicity and provide new mechanistic insights about vaccines.

Show MeSH
Related in: MedlinePlus