Abstract
The evolution of the H5N1 highly pathogenic avian influenza virus (HPAIV) has resulted in high sequence variations and diverse antigenic properties in circulating viral isolates. We investigated immune responses induced by HA DNA vaccines of two contemporary H5N1 HPAIV isolates, A/bar-headed goose/Qinghai/3/2005 (QH) and A/chicken/Shanxi/2/2006 (SX) respectively, against the homologous as well as the heterologous virus isolate for comparison. Characterization of antibody responses induced by immunization with QH-HA and SX-HA DNA vaccines showed that the two isolates are antigenically distinctive. Interestingly, after immunization with the QH-HA DNA vaccine, subsequent boosting with the SX-HA DNA vaccine significantly augmented antibody responses against the QH isolate but only induced low levels of antibody responses against the SX isolate. Conversely, after immunization with the SX-HA DNA vaccine, subsequent boosting with the QH-HA DNA vaccine significantly augmented antibody responses against the SX isolate but only induced low levels of antibody responses against the QH isolate. In contrast to the antibody responses, cross-reactive T cell responses are readily detected between these two isolates at similar levels. These results indicate the existence of original antigenic sin (OAS) between concurrently circulating H5N1 HPAIV strains, which may need to be taken into consideration in vaccine development against the potential H5N1 HPAIV pandemic.
Highlights
Influenza virus infection causes serious respiratory illness, and seasonal human influenza epidemics are estimated to result in about 40,000 deaths and over 200,000 hospitalizations annually in the U.S alone and up to 1.5 million deaths worldwide [1,2]
We investigated immune responses induced by HA DNA vaccines of two H5N1 highly pathogenic avian influenza virus (HPAIV) isolates, A/bar-headed goose/Qinghai/3/2005 (QH) and A/chicken/Shanxi/2/2006 (SX), that are representatives of two HPAIV antigenic lineages clade 2.2 and clade 7 respectively [19]
In agreement with the results from ELISA studies, antibodies induced by QH-HA DNA vaccine exhibit hemagglutination inhibition (HAI) activity against the QH virus (Figure 2c) but not the SX virus (Figure 2d), whereas antibodies induced by the SX-HA DNA vaccine exhibit HAI activity against the SX virus (Figure 2d) but not the QH virus (Figure 2c)
Summary
Influenza virus infection causes serious respiratory illness, and seasonal human influenza epidemics are estimated to result in about 40,000 deaths and over 200,000 hospitalizations annually in the U.S alone and up to 1.5 million deaths worldwide [1,2]. Influenza A viruses are further divided into different subtypes based on their surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA). Only 3 HA subtypes (H1–H3) and 2 NA subtypes (N1– N2) have been circulated and caused pandemic and seasonal influenza epidemics. The rapid spread of the new H1N1 influenza virus demonstrates that a new human influenza pandemic of zoonotic origin poses a real threat to the public health
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