Induction of cross-protection against influenza A virus by DNA prime-intranasal protein boost strategy based on nucleoprotein

Luo, Jian; Zheng, Dan; Zhang, Wenjie; Fang, Fang; Wang, Hanzhong; Sun, Yingxian; Ding, Yahong; Xu, Chengfei; Chen, Quanjiao; Zhang, Hongbo; Ding, Huang; Sun, Bing; Chen, Ze

doi:10.1186/1743-422x-9-286

Cited by 24 publications

(19 citation statements)

References 49 publications

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“…The H1 protein identity is closer to 80% conserved for the last two decades suggesting that protein sequence conservation could contribute to these effects. Indeed, vaccines based on NP and/or M have been proposed to take advantage of this conservation [3,4,38]. Development of a vaccine based on enhancing NP+M responses would be a logical extension of these data, though it remains unclear whether the protein target of CD4 T cells impacts their protective capacity or whether memory Th1-like CD4 T cells are, in fact, protective in aged humans.…”

Section: Discussionmentioning

confidence: 99%

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Vaccine-Induced Boosting of Influenza Virus-Specific CD4 T Cells in Younger and Aged Humans

et al. 2013

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Current yearly influenza virus vaccines induce strain-specific neutralizing antibody (NAb) responses providing protective immunity to closely matched viruses. However, these vaccines are often poorly effective in high-risk groups such as the elderly and challenges exist in predicting yearly or emerging pandemic influenza virus strains to include in the vaccines. Thus, there has been considerable emphasis on understanding broadly protective immunological mechanisms for influenza virus. Recent studies have implicated memory CD4 T cells in heterotypic immunity in animal models and in human challenge studies. Here we examined how influenza virus vaccination boosted CD4 T cell responses in younger versus aged humans. Our results demonstrate that while the magnitude of the vaccine-induced CD4 T cell response and number of subjects responding on day 7 did not differ between younger and aged subjects, fewer aged subjects had peak responses on day 14. While CD4 T cell responses were inefficiently boosted against NA, both HA and especially nucleocaspid protein- and matrix-(NP+M) specific responses were robustly boosted. Pre-existing CD4 T cell responses were associated with more robust responses to influenza virus NP+M, but not H1 or H3. Finally pre-existing strain-specific NAb decreased the boosting of CD4 T cell responses. Thus, accumulation of pre-existing influenza virus-specific immunity in the form of NAb and cross-reactive T cells to conserved virus proteins (e.g. NP and M) over a lifetime of exposure to infection and vaccination may influence vaccine-induced CD4 T cell responses in the aged.

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Section: Discussionmentioning

confidence: 99%

“…There has been considerable recent interest in influenza virus-specific CD4 T cells as potential targets for heterosubtypic immunity [2-4]. In animal models Th1-like memory CD4 T cells can provide robust heterotypic immunity [5,6].…”

Section: Introductionmentioning

confidence: 99%

Vaccine-Induced Boosting of Influenza Virus-Specific CD4 T Cells in Younger and Aged Humans

et al. 2013

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“…For example, Lo et al (30) constructed NP-based DNA and adenovirus vaccines and showed that a DNA prime-adenovirus boost strategy greatly improved the cross-protection induced by NP-based vaccines. Luo et al (49) found that the immune response induced in mice by the NP DNA vaccine was enhanced by an intranasal boost with recombinant NP (rNP) protein. The prime-boost strategy provided protection not only against the homologous virus but also cross-protection against a heterosubtypic H9N2 strain.…”

mentioning

confidence: 99%

Protective Efficacy of the Conserved NP, PB1, and M1 Proteins as Immunogens in DNA- and Vaccinia Virus-Based Universal Influenza A Virus Vaccines in Mice

Wang

Deng

et al. 2015

Clin Vaccine Immunol

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bThe conventional hemagglutinin (HA)-and neuraminidase (NA)-based influenza vaccines need to be updated most years and are ineffective if the glycoprotein HA of the vaccine strains is a mismatch with that of the epidemic strain. Universal vaccines targeting conserved viral components might provide cross-protection and thus complement and improve conventional vaccines. In this study, we generated DNA plasmids and recombinant vaccinia viruses expressing the conserved proteins nucleoprotein (NP), polymerase basic 1 (PB1), and matrix 1 (M1) from influenza virus strain A/Beijing/30/95 (H3N2). BALB/c mice were immunized intramuscularly with a single vaccine based on NP, PB1, or M1 alone or a combination vaccine based on all three antigens and were then challenged with lethal doses of the heterologous influenza virus strain A/PR/8/34 (H1N1). Vaccines based on NP, PB1, and M1 provided complete or partial protection against challenge with 1.7 50% lethal dose (LD 50 ) of PR8 in mice. Of the three antigens, NP-based vaccines induced protection against 5 LD 50 and 10 LD 50 and thus exhibited the greatest protective effect. Universal influenza vaccines based on the combination of NP, PB1, and M1 induced a strong immune response and thus might be an alternative approach to addressing future influenza virus pandemics.T he conventional influenza vaccines that are available currently to prevent seasonal flu outbreaks depend mainly on the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) (1, 2). However, HA-and NA-based conventional influenza vaccines sometimes fail to prevent flu epidemics because the HA and/or NA in the vaccine strains is a mismatch with that in circulating virus strains (3-7). Universal influenza vaccines (UIVs) that induce effective and long-term cross-protection and address the risk of mismatch may overcome the shortcomings of conventional influenza vaccines. Therefore, the development of a UIV capable of inducing long-term immunity and cross-protection remains a priority in influenza vaccine research (8).Influenza viruses are classified as type A, B, or C based on their nucleoprotein (NP) and matrix protein (M). Among the three subtypes, influenza A virus has been the target of UIVs, because the diverse influenza A strains frequently trigger influenza epidemics and pandemics. A previous study indicated that humans mount a good response to the highly conserved internal proteins NP, M1, and polymerase basic 1 (PB1) of influenza A virus (9); therefore, these highly conserved influenza A virus antigens are the basis of UIVs. Multiple studies have investigated the potential of NP (10-13), matrix protein 1 (M1) (14-17), and ion channel (M2, mainly M2e) (18-27) as alternative vaccine antigens for the prevention of seasonal and pandemic flu outbreaks. PB1 has also shown protective potential but requires further investigation for inclusion in UIVs. Košík et al. (28) constructed a DNA vaccine based on PB1, which provided some protective immunity in a mouse model. We previously constructed DNA vaccines ...

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“…Optimal systemic antibody and T cell responses were achieved by immunization of mice with a subunit influenza vaccine containing a saponin-derived GPI-0100 adjuvant through intranasal prime-intramuscular boost strategies [101]. DNA prime and protein boost of NP is a practical way of improving cross-protective immunity against influenza A virus infection [102]. …”

Section: Advancements In the Development Of Subunit Influenza Vaccmentioning

confidence: 99%

Advancements in the development of subunit influenza vaccines

Zhang

Zheng

et al. 2015

Microbes and Infection

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The ongoing threat of influenza epidemics and pandemics has emphasized the importance of developing safe and effective vaccines against infections from divergent influenza viruses. In this review, we first introduce the structure and life cycle of influenza A viruses, describing major influenza A virus-caused pandemics. We then compare different types of influenza vaccines and discuss current advancements in the development of subunit influenza vaccines, particularly those based on nucleoprotein (NP), extracellular domain of matrix protein 2 (M2e) and hemagglutinin (HA) proteins. We also illustrate potential strategies for improving the efficacy of subunit influenza vaccines.

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Induction of cross-protection against influenza A virus by DNA prime-intranasal protein boost strategy based on nucleoprotein

Cited by 24 publications

References 49 publications

Vaccine-Induced Boosting of Influenza Virus-Specific CD4 T Cells in Younger and Aged Humans

Vaccine-Induced Boosting of Influenza Virus-Specific CD4 T Cells in Younger and Aged Humans

Protective Efficacy of the Conserved NP, PB1, and M1 Proteins as Immunogens in DNA- and Vaccinia Virus-Based Universal Influenza A Virus Vaccines in Mice

Advancements in the development of subunit influenza vaccines

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