MHV68 Latency Modulates the Host Immune Response to Influenza A Virus

AbstractThis study describes the associations between fecal microbiota and vaccine response variability in pigs, using 98 piglets vaccinated against the influenza A virus at 28 days of age (D28) with a booster at D49. Immune response to the vaccine is measured at D49, D56, D63, and D146 by serum levels of IAV-specific IgG and assays of hemagglutination inhibition (HAI). Analysis of the pre-vaccination microbiota characterized by 16S rRNA gene sequencing of fecal DNA reveals a higher vaccine response in piglets with a richer microbiota, and shows that 23 operational taxonomic units (OTUs) are differentially abundant between high and low IAV-specific IgG producers at D63. A stronger immune response is linked with OTUs assigned to the genus Prevotella and family Muribaculaceae, and a weaker response is linked with OTUs assigned to the genera Helicobacter and Escherichia-Shigella. A set of 81 OTUs accurately predicts IAV-specific IgG and HAI titer levels at all time points, highlighting early and late associations between pre-vaccination fecal microbiota composition and immune response to the vaccine.

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Impact of Influenza A Virus Shutoff Proteins on Host Immune Responses

Vaccines ◽

10.3390/vaccines9060629 ◽

2021 ◽

Vol 9 (6) ◽

pp. 629

Author(s):

Megan M. Dunagan ◽

Kala Hardy ◽

Toru Takimoto

Keyword(s):

Immune Response ◽

Immune Responses ◽

Influenza A Virus ◽

Influenza A ◽

Human Populations ◽

Lymphocyte Migration ◽

Host Immune Responses ◽

Mhc Molecules ◽

The Impact

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X and NS1, which antagonize the host innate immune response. By transcriptomic analysis, we previously showed that PA-X is a major contributor for general shutoff, while shutoff active NS1 specifically inhibits the expression of host cytokines, MHC molecules, and genes involved in innate immunity in cultured human cells. So far, the impact of these shutoff proteins in the acquired immune response in vivo has not been determined in detail. In this study, we analyzed the effects of PA-X and NS1 shutoff activities on immune response using recombinant influenza A/California/04/2009 viruses containing mutations affecting the expression of shutoff active PA-X and NS1 in a mouse model. Our data indicate that the virus without shutoff activities induced the strongest T and B cell responses. Both PA-X and NS1 reduced host immune responses, but shutoff active NS1 most effectively suppressed lymphocyte migration to the lungs, antibody production, and the generation of IAV specific CD4+ and CD8+ T cells. NS1 also prevented the generation of protective immunity against a heterologous virus challenge. These data indicate that shutoff active NS1 plays a major role in suppressing host immune responses against IAV infection.

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238 Innate immune response triggered by influenza A virus is negatively regulated by suppressor of cytokine signaling (SOCS)1 and SOCS3 through a RIG-I/IFNAR1-dependent pathway

Cytokine ◽

10.1016/j.cyto.2008.07.303 ◽

2008 ◽

Vol 43 (3) ◽

pp. 296

Author(s):

Julien Pothlichet ◽

Michel Chignard ◽

Mustapha Si-Tahar

Keyword(s):

Immune Response ◽

Influenza A Virus ◽

Innate Immune Response ◽

Influenza A ◽

Innate Immune ◽

Cytokine Signaling ◽

Suppressor Of Cytokine Signaling ◽

Dependent Pathway

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Response Modifiers: Tweaking the Immune Response Against Influenza A Virus

Frontiers in Immunology ◽

10.3389/fimmu.2019.00809 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 5

Author(s):

Husni Elbahesh ◽

Thomas Gerlach ◽

Giulietta Saletti ◽

Guus F. Rimmelzwaan

Keyword(s):

Immune Response ◽

Influenza A Virus ◽

Influenza A

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Immunogenicity, Boostability, and Sustainability of the Immune Response after Vaccination against Influenza A Virus (H1N1) 2009 in a Healthy Population

Clinical and Vaccine Immunology ◽

10.1128/cvi.05046-11 ◽

2011 ◽

Vol 18 (9) ◽

pp. 1401-1405 ◽

Cited By ~ 36

Author(s):

Elisabeth Huijskens ◽

John Rossen ◽

Paul Mulder ◽

Ruud van Beek ◽

Hennie van Vugt ◽

...

Keyword(s):

Immune Response ◽

Influenza Virus ◽

Influenza A Virus ◽

Influenza A ◽

Seasonal Influenza ◽

Virus H1n1 ◽

Prospective Longitudinal Study ◽

Virus Vaccination ◽

Short Period ◽

Prospective Longitudinal

ABSTRACTThe emergence of a new influenza A virus (H1N1) variant in 2009 led to a worldwide vaccination program, which was prepared in a relatively short period of time. This study investigated the humoral immunity against this virus before and after vaccination with a 2009 influenza A virus (H1N1) monovalent MF59-adjuvanted vaccine, as well as the persistence of vaccine-induced antibodies. Our prospective longitudinal study included 498 health care workers (mean age, 43 years; median age, 44 years). Most (89%) had never or only occasionally received a seasonal influenza virus vaccine, and 11% were vaccinated annually (on average, for >10 years). Antibody titers were determined by a hemagglutination inhibition (HI) assay at baseline, 3 weeks after the first vaccination, and 5 weeks and 7 months after the second vaccination. Four hundred thirty-five persons received two doses of the 2009 vaccine. After the first dose, 79.5% developed a HI titer of ≥40. This percentage increased to 83.3% after the second dose. Persistent antibodies were found in 71.9% of the group that had not received annual vaccinations and in 43.8% of the group that had received annual vaccinations. The latter group tended to have lower HI titers (P=0.09). With increasing age, HI titers decreased significantly, by 2.4% per year. A single dose of the 2009 vaccine was immunogenic in almost 80% of the study population, whereas an additional dose resulted in significantly increased titers only in persons over 50. Finally, a reduced HI antibody response against the 2009 vaccine was found in adults who had previously received seasonal influenza virus vaccination. More studies on the effect of yearly seasonal influenza virus vaccination on the immune response are warranted.

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