Cross reactivity of serum antibody responses elicited by DNA vaccines expressing HA antigens from H1N1 subtype influenza vaccines in the past 30 years

Almansour, Iman; Chen, Huaiqing; Wang, Shixia; Lu, Shan

doi:10.4161/hv.25735

Cited by 9 publications

(9 citation statements)

References 38 publications

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“…HA is the major protective antigen in clinically licensed inactivated and live-attenuated influenza vaccines. DNA vaccines expressing HA have been shown to be immunogenic in eliciting HA-specific antibodies in both animal and human studies (2,(30)(31)(32)(33)(34). The expression of HA antigen by pH1HA used in the current study was confirmed by Western blot and its immunogenicity to elicit HA-specific antibody response was verified in a pilot mouse study (data not shown).…”

Section: Dna Vaccine Plasmid Induces Expression Of Aim2 Caspase-1 Anmentioning

confidence: 57%

Identification of Aim2 as a Sensor for DNA Vaccines

Suschak

Wang

Fitzgerald

et al. 2015

The Journal of Immunology

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Recent human study data has re-established the value of DNA vaccines, especially in priming high-level antigen-specific antibody responses, but also raised questions about the mechanisms responsible for such effects. Whereas previous reports have shown involvement of downstream signaling molecules in the innate immune system, the current study investigated the role of Aim2 as a sensor for DNA vaccines. The Aim2 inflammasome directs maturation of the pro-inflammatory cytokines IL-1β and IL-18 and an inflammatory form of cell death called pyroptosis. Both the humoral and cellular antigen-specific adaptive responses were significantly reduced in Aim2−/− mice in an IL-1β/IL-18 independent manner after DNA vaccination. Surprisingly, Aim2−/− mice also exhibited significantly lower levels of IFN-α/β at the site of injection. These results indicate a previously unreported link between DNA vaccine induced pyroptotic cell death and vaccine immunogenicity that is instrumental in shaping the antigen specific immune response to DNA vaccines.

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Section: Dna Vaccine Plasmid Induces Expression Of Aim2 Caspase-1 Anmentioning

confidence: 57%

Identification of Aim2 as a Sensor for DNA Vaccines

Suschak

Wang

Fitzgerald

et al. 2015

The Journal of Immunology

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“…To confirm these results with a DNA vaccine expressing a viral immunogen, we vaccinated mice with DNA vaccine pH1HA expressing the HA antigen of the influenza A virus which was responsible for the H1N1 pandemic in 2009. As HA is highly immunogenic and is the major protective antigen in clinically licensed inactivated and live-attenuated influenza vaccines, HA DNA vaccines provide a sensitive study model (15, 16, 18, 30, 36–38) to detect the impact of innate immunity on a clinically relevant immunogen.…”

Section: Resultsmentioning

confidence: 99%

A cGAS-Independent STING/IRF7 Pathway Mediates the Immunogenicity of DNA Vaccines

Suschak

Wang

Fitzgerald

et al. 2016

The Journal of Immunology

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It is known since the discovery of DNA vaccines more than 20 years ago that DNA vaccines can function as adjuvants. Our recent study reported the involvement of Aim2 as the sensor of DNA vaccines in eliciting antigen-specific antibody responses. Our findings indicated the presence of previously unrecognized innate immune response pathways in addition to the TLR9 pathway, which is mainly activated by the CpG motifs of DNA vaccines. Our data further demonstrated the requirement of type I IFN in DNA vaccine-induced immune responses via the Aim2 pathway, but the exact downstream molecular mechanism was not characterized. In the current study, we investigated the roles of the putative DNA sensor cyclic GMP-AMP synthase (cGas), as well as the downstream interferon regulatory factors (Irf) 3 and 7 in type I IFN induction and antigen-specific immune responses elicited by DNA vaccination. Our results showed that DNA vaccine induced, Irf7-dependent signaling, as part of the Sting pathway, was critical for generation of both innate cytokine signaling and antigen-specific B and T cell responses. In contrast, Irf3 was not as critical as expected in this pathway and more surprisingly, immune responses elicited by DNA vaccines were not cGas dependent in vivo. Data presented in the current report provide more details on the innate immune mechanisms involved in DNA vaccination and further enrich our understanding on the potential utility of DNA vaccines in generating antigen-specific immune responses.

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“…Pseudotype viruses (psv) were constructed from the following H1N1 influenza strains: A/Brazil/78(BZ78), A/Chile/1/83(CH83), A/Taiwan/1/86(TW86), A/Texas/36/91(TX91), A/Bayern/7/95(BY95), A/Beijing/262/95(BJ95), and A/Solomon Islands/3/06(SI06) (Table 1). The pseudovirus titers were determined by single-round infection of 293A cells [26]. …”

Section: Methodsmentioning

confidence: 99%

Antigen-specific H1N1 influenza antibody responses in acute respiratory tract infections and their relation to influenza infection and disease course

Haran¹,

Hoaglin

Chen

et al. 2014

Journal of Clinical Virology

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Background Early antibody responses to influenza infection are important in both clearance of virus and fighting the disease. Acute influenza antibody titers directed toward H1-antigens and their relation to infection type and patient outcomes have not been well investigated. Objective Using hemagglutination inhibition (HI) assays, we aimed to characterize the H1-specific antibody titers in patients with influenza infection or another respiratory infection before and after the H1N1-pandemic influenza outbreak. Among patients with acute influenza infection we related duration of illness, severity of symptoms, and need for hospitalization to antibody titers. Methods There were 134 adult patients (average age 34.7) who presented to an urban academic emergency department (ED) from October through March during the 2008–2011 influenza seasons with symptoms of fever and a cough. Nasal aspirates were tested by viral culture, and peripheral blood serum was run in seven H1-subtype HI assays. Results Acutely infected influenza patients had markedly lower antibody titers for six of the seven pseudotype viruses. For the average over the seven titers (log units, base 2) their mean was 7.24 (95% CI 6.88, 7.61) compared with 8.60 (95% CI 8.27, 8.92) among patients who had a non-influenza respiratory illness, p < 0.0001. Among patients with seasonal influenza infection, titers of some antibodies correlated with severity of symptoms and with total duration of illness (p < 0.02). Conclusion In patients with acute respiratory infections, lower concentrations of H1-influenza-specific antibodies were associated with influenza infection. Among influenza-infected patients, higher antibody titers were present in patients with a longer duration of illness and with higher severity-of-symptom scores.

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Cross reactivity of serum antibody responses elicited by DNA vaccines expressing HA antigens from H1N1 subtype influenza vaccines in the past 30 years

Cited by 9 publications

References 38 publications

Identification of Aim2 as a Sensor for DNA Vaccines

Identification of Aim2 as a Sensor for DNA Vaccines

A cGAS-Independent STING/IRF7 Pathway Mediates the Immunogenicity of DNA Vaccines

Antigen-specific H1N1 influenza antibody responses in acute respiratory tract infections and their relation to influenza infection and disease course

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