Immunization with live virus vaccine protects highly susceptible DBA/2J mice from lethal influenza A H1N1 infection

Dengler, Leonie; May, Mathias; Wilk, Esther; Bahgat, Mahmoud Mohamed; Schughart, Klaus

doi:10.1186/1743-422x-9-212

Cited by 7 publications

(6 citation statements)

References 28 publications

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“…The robust response of DBA.2 mice with an approximately 1000-fold acute increase in SAA levels at 3 dpi implies that DBA.2 mice are much more susceptible to influenza virus infections than C57BL/2 or Swiss-Webster mice. This observation has also been made by others (Dengler et al, 2012; Pica et al, 2011). DBA.2 mice offer the additional advantage of being susceptible to influenza viruses that have not been mouse-adapted (Boon et al, 2010; Kim et al, 2013).…”

Section: Discussionsupporting

confidence: 88%

Serum amyloid A (SAA) is an early biomarker of influenza virus disease in BALB/c, C57BL/2, Swiss-Webster, and DBA.2 mice

2016

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Assessment of influenza virus disease progression and efficacy of antiviral therapy in the widely used mouse models relies mostly on body weight loss and lung virus titers as markers of disease. However, both parameters have their shortcomings. Therefore, the aim of our study was to find non-invasive markers in the murine model of severe influenza that could detect disease early and predict disease outcome. BALB/c mice were lethally infected with influenza A(H1N1)pdm09 virus and serum samples were collected at various time points. Enzyme-linked immunosorbent assays were performed to quantify amounts of serum amyloid A (SAA), C-reactive protein, complement 3, transferrin, corticosterone, prostaglandin E2, H2O2, and alpha-2,6-sialyltransferase. We found that SAA was the most promising candidate with levels acutely and temporarily elevated by several hundred-fold 3 days post virus inoculation. Upon treatment with oseltamivir phosphate, levels of SAA were significantly decreased. High levels of SAA were associated with poor disease prognosis, whereas body weight loss was not as a reliable predictor of disease outcome. SAA levels were also transiently increased in BALB/c mice infected with influenza A(H3N2) and influenza B virus, as well as in C57BL/2, Swiss-Webster, and DBA.2 mice infected with influenza A(H1N1)pdm09 virus. High levels of SAA often, but not always, were associated with disease outcome in these other influenza virus mouse models. Therefore, SAA represents a valid biomarker for influenza disease detection in all tested mouse strains but its prognostic value is limited to BALB/c mice infected with influenza A(H1N1)pdm09 virus.

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Section: Discussionsupporting

confidence: 88%

Serum amyloid A (SAA) is an early biomarker of influenza virus disease in BALB/c, C57BL/2, Swiss-Webster, and DBA.2 mice

2016

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“…1C and 1D), similar to BALB/c mice. This result suggests that the high susceptibility of DBA/2 mice to influenza viruses may not be due to impaired immune responses against influenza viruses (Dengler et al, 2012) and that the DBA/2 mouse model may be otherwise comparable with other mouse models.…”

Section: Pathogenicity Of the Ph1n1 K/09 Virus In Balb/c Versus Dba/2...mentioning

confidence: 73%

“…However, evaluation of antiviral drug efficacy with a mouse-adapted virus in vivo can be complicated by genetic changes in the virus genome during the mouse adaptation process (Sakabe et al, 2011;Zhu et al, 2012). Thus, DBA/2 mice, which do not require prior adaptation of most influenza viruses, have been actively utilized in studies on the functions of influenza viral proteins (Hai et al, 2010), potentials of antibody therapy (Boon et al, 2010;Kashyap et al, 2010), and vaccine efficacy (Solorzano et al, 2010;Dengler et al, 2012). Using an un- adapted virus is critically important for testing the efficacy of anti-influenza drugs against human-infecting viruses, particularly during the drug development stage, as the antiviral effect of the drug should not be against the mouseadapted virus but ultimately against the original humaninfecting virus.…”

Section: Introductionmentioning

confidence: 99%

DBA/2 mouse as an animal model for anti-influenza drug efficacy evaluation

et al. 2013

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Influenza viruses are seasonally recurring human pathogens. Vaccines and antiviral drugs are available for influenza. However, the viruses, which often change themselves via antigenic drift and shift, demand constant efforts to update vaccine antigens every year and develop new agents with broad-spectrum antiviral efficacy. An animal model is critical for such efforts. While most human influenza viruses are unable to kill BALB/c mice, some strains have been shown to kill DBA/2 mice without prior adaptation. Therefore, in this study, we explored the feasibility of employing DBA/2 mice as a model in the development of anti-influenza drugs. Unlike the BALB/c strain, DBA/2 mice were highly susceptible and could be killed with a relatively low titer (50% DBA/2 lethal dose = 10(2.83) plaque-forming units) of the A/Korea/01/2009 virus (2009 pandemic H1N1 virus). When treated with a neuraminidase inhibitor, oseltamivir phosphate, infected DBA/2 mice survived until 14 days post-infection. The reduced morbidity of the infected DBA/2 mice was also consistent with the oseltamivir treatment. Taking these data into consideration, we propose that the DBA/2 mouse is an excellent animal model to evaluate antiviral efficacy against influenza infection and can be further utilized for combination therapies or bioactivity models of existing and newly developed anti-influenza drugs.

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“…However, as we chose to use a wild-type human isolate without mouse adaptation in these studies, the DBA/2J model was used, based on the results of the comparison studies. The DBA/2J model has been used extensively in influenza virus studies and has been shown to be a suitable, well characterized model to evaluate influenza vaccines [ 26 – 30 ], although the mechanism of susceptibility to H7N9 infection may not be as well understood as in the BALB/c mouse model.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and Protective Efficacy of a Vero Cell Culture-Derived Whole-Virus H7N9 Vaccine in Mice and Guinea Pigs

et al. 2015

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BackgroundA novel avian H7N9 virus with a high case fatality rate in humans emerged in China in 2013. We evaluated the immunogenicity and protective efficacy of a candidate Vero cell culture-derived whole-virus H7N9 vaccine in small animal models.MethodsAntibody responses induced in immunized DBA/2J mice and guinea pigs were evaluated by hemagglutination inhibition (HI), microneutralization (MN), and neuraminidase inhibition (NAi) assays. T-helper cell responses and IgG subclass responses in mice were analyzed by ELISPOT and ELISA, respectively. Vaccine efficacy against lethal challenge with wild-type H7N9 virus was evaluated in immunized mice. H7N9-specific antibody responses induced in mice and guinea pigs were compared to those induced by a licensed whole-virus pandemic H1N1 (H1N1pdm09) vaccine.ResultsThe whole-virus H7N9 vaccine induced dose-dependent H7N9-specific HI, MN and NAi antibodies in mice and guinea pigs. Evaluation of T-helper cell responses and IgG subclasses indicated the induction of a balanced Th1/Th2 response. Immunized mice were protected against lethal H7N9 challenge in a dose-dependent manner. H7N9 and H1N1pdm09 vaccines were similarly immunogenic.ConclusionsThe induction of H7N9-specific antibody and T cell responses and protection against lethal challenge suggest that the Vero cell culture-derived whole-virus vaccine would provide an effective intervention against the H7N9 virus.

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Immunization with live virus vaccine protects highly susceptible DBA/2J mice from lethal influenza A H1N1 infection

Cited by 7 publications

References 28 publications

Serum amyloid A (SAA) is an early biomarker of influenza virus disease in BALB/c, C57BL/2, Swiss-Webster, and DBA.2 mice

Serum amyloid A (SAA) is an early biomarker of influenza virus disease in BALB/c, C57BL/2, Swiss-Webster, and DBA.2 mice

DBA/2 mouse as an animal model for anti-influenza drug efficacy evaluation

Immunogenicity and Protective Efficacy of a Vero Cell Culture-Derived Whole-Virus H7N9 Vaccine in Mice and Guinea Pigs

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