In vitro evidence that commercial influenza vaccines are not similar in their ability to activate human T cell responses

Co, Mary Dawn T.; Orphin, Laura; Cruz, John; Pazoles, Pamela P.; Green, Karin M.; Potts, James; Leporati, Anita M.; Babon, Jenny Aurielle B.; Evans, James E.; Ennis, Francis A.; Terajima, Masanori

doi:10.1016/j.vaccine.2008.09.092

Cited by 50 publications

(50 citation statements)

References 43 publications

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“…The ability of commercially available influenza vaccines to induce human T-cell responses may vary depending on the internal protein contents of vaccines from different manufacturers (12). Here we showed that TIV (GlaxoSmithKline) induced HLA-A2/M1 58-66 -tetramer ϩ CD8 ϩ T cells in 20% of HLA-2-positive individuals, as this vaccine contains a relatively high level of M protein (11).…”

Section: Cross-response Of Bulk Ctls Against Pdmh1n1 In Healthy Indivmentioning

confidence: 79%

Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-React against 2009 Pandemic H1N1 Influenza Virus

Mao

Zheng

et al. 2010

J Virol

138

127

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While few children and young adults have cross-protective antibodies to the pandemic H1N1 2009 (pdmH1N1) virus, the illness remains mild. The biological reasons for these epidemiological observations are unclear. In this study, we demonstrate that the bulk memory cytotoxic T lymphocytes (CTLs) established by seasonal influenza viruses from healthy individuals who have not been exposed to pdmH1N1 can directly lyse pdmH1N1-infected target cells and produce gamma interferon (IFN-␥) and tumor necrosis factor alpha (TNF-␣). Using influenza A virus matrix protein 1 (M1 58-66 ) epitope-specific CTLs isolated from healthy HLA-A2 ؉ individuals, we further found that M1 58-66 epitope-specific CTLs efficiently killed both M1 58-66 peptide-pulsed and pdmH1N1-infected target cells ex vivo. These M1 58-66 -specific CTLs showed an effector memory phenotype and expressed CXCR3 and CCR5 chemokine receptors. Of 94 influenza A virus CD8 T-cell epitopes obtained from the Immune Epitope Database (IEDB), 17 epitopes are conserved in pdmH1N1, and more than half of these conserved epitopes are derived from M1 protein. In addition, 65% (11/17) of these epitopes were 100% conserved in seasonal influenza vaccine H1N1 strains during the last 20 years. Importantly, seasonal influenza vaccination could expand the functional M1 58-66 epitope-specific CTLs in 20% (4/20) of HLA-A2 ؉ individuals. Our results indicated that memory CTLs established by seasonal influenza A viruses or vaccines had cross-reactivity against pdmH1N1. These might explain, at least in part, the unexpected mild pdmH1N1 illness in the community and also might provide some valuable insights for the future design of broadly protective vaccines to prevent influenza, especially pandemic influenza.

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Section: Cross-response Of Bulk Ctls Against Pdmh1n1 In Healthy Indivmentioning

confidence: 79%

Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-React against 2009 Pandemic H1N1 Influenza Virus

Mao

Zheng

et al. 2010

J Virol

138

127

View full text Add to dashboard Cite

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“…The somewhat greater antibody responses to ADV might not translate into greater protection as subunit vaccines potentially induce lesser cellular immune responses. 41 Neutralizing antibody assays would ideally have been performed with all 3 viruses and might have shed light on the elevated baseline B titers. Finally, we recognize that the seroprotection threshold (HAI titers ≥ 40) conventionally used to evaluate responses may not accurately predict protection in elderly adults, with greater antibody titers and cellular immune responses being required for protection.…”

Section: Discussionmentioning

confidence: 99%

Safety, immunogenicity, and tolerability of three influenza vaccines in older adults

Scheifele

McNeil

Ward

et al. 2013

Human Vaccines & Immunotherapeutics

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“…In support of this idea, other studies have shown that TLR7 is important for the induction of a protective memory response against influenza whole inactivated vaccine (18,34,35), while split vaccines lacking intact RNAs are defective in inducing a protective antibody response (34). In addition, Co and colleagues showed that a seasonal split vaccine activated human T cells more efficiently than a subunit vaccine, which contains only the highly purified surface antigens HA and neuraminidase (NA) (11). In a separate study, Kasturi and colleagues showed that purified HA alone did not elicit virusneutralizing antibody titers, whereas the addition of a TLR7 ligand to HA increased antibody production in mice (30).…”

Section: Fig 3 Tlr7mentioning

confidence: 94%

TLR7 Recognition Is Dispensable for Influenza Virus A Infection but Important for the Induction of Hemagglutinin-Specific Antibodies in Response to the 2009 Pandemic Split Vaccine in Mice

Jeisy-Scott

Kim

Davis

et al. 2012

J Virol

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Recognition of pathogen-associated molecular patterns by pattern recognition receptors of the innate immune system is crucial for the initiation of innate and adaptive responses and for immunological memory. We investigated the role of TLR7 in the induction of adaptive immunity and long-term memory following influenza virus infection and vaccination in C57BL/6 mice. During infection with influenza A/PR8/34 virus, the absence of either TLR7 or MyD88 leads to reduced virus-specific antibodies in the serum and antibody-secreting cells in their secondary lymphoid organs, particularly in bone marrow. In spite of this, the absence of TLR7/MyD88 signaling did not impair the production of protective antibodies. Following immunization with the 2009 pandemic inactivated split vaccine, TLR7 −/− mice had significantly lower levels of germinal center formation, antibody-secreting cells, and circulating influenza virus-specific antibodies than control animals. Consequently, TLR7 −/− mice failed to develop protective immunological memory upon challenge. Furthermore, the immunogenicity of the split vaccine was likely due to TLR7 recognition of virion RNA, as its removal from the split vaccine significantly reduced the levels of influenza virus-specific antibodies and compromised the vaccine protective efficacy in mice. Taken together, our data demonstrate that TLR7 plays an important role in vaccine-induced humoral immune responses to influenza virus through the interaction with viral RNA present in the split vaccine.

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In vitro evidence that commercial influenza vaccines are not similar in their ability to activate human T cell responses

Cited by 50 publications

References 43 publications

Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-React against 2009 Pandemic H1N1 Influenza Virus

Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-React against 2009 Pandemic H1N1 Influenza Virus

Safety, immunogenicity, and tolerability of three influenza vaccines in older adults

TLR7 Recognition Is Dispensable for Influenza Virus A Infection but Important for the Induction of Hemagglutinin-Specific Antibodies in Response to the 2009 Pandemic Split Vaccine in Mice

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