Protective immunity by intramuscular injection of low doses of influenza virus DNA vaccines

Ulmer, Jeffrey M.; Deck, R. Randall; DeWitt, Corrille M.; Friedman, Arthur; Donnelly, John; Liu, Margaret A.

doi:10.1016/0264-410x(94)90081-7

Cited by 161 publications

(62 citation statements)

References 11 publications

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“…We selected the doses of 10 and 100 g of DNA for immunization to evaluate the comparative protective efficacy of two different constructs based on a very thorough and extensive review of all the reports describing different doses of DNA vaccine used for HA via the i.m. route of immunization (42)(43)(44). We also tested 20-and 40-g doses, and the responses observed were intermediate between those of the 10-and 100-g doses (data not shown).…”

Section: Discussionmentioning

confidence: 99%

The Hybrid Cytomegalovirus Enhancer/Chicken β-Actin Promoter along with Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element Enhances the Protective Efficacy of DNA Vaccines

Garg

Oran

Hon

et al. 2004

The Journal of Immunology

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DNA vaccines represent a novel and powerful alternative to conventional vaccine approaches. They are extremely stable and can be produced en masse at low cost; more importantly, DNA vaccines against emerging pathogens or bioterrorism threats can be quickly constructed based solely upon the pathogen’s genetic code. The main drawback of DNA vaccines is that they often induce lower immune responses than traditional vaccines, particularly in nonrodent species. Thus, improving the efficacy of DNA vaccines is a critical issue in vaccine development. In this study we have enhanced the efficacy of DNA vaccines by adopting strategies that increase gene expression. We generated influenza-hemagglutinin (HA)-encoding DNA vaccines that contain the hybrid CMV enhancer/chicken β-actin (CAG) promoter and/or the mRNA-stabilizing post-transcriptional regulatory element from the woodchuck hepatitis virus (WPRE). Mice were immunized with these DNA vaccines, and the influenza-HA-specific cellular and humoral immune responses were compared with a conventional, HA-encoding DNA vaccine whose gene expression was driven by the CMV immediate-early promoter (pCMV-HA). CAG promoter-driven DNA vaccines elicited significantly higher humoral and cellular immune responses compared with the pCMV-HA vaccine. DNA vaccines consisting of both CAG and WPRE elements (pCAG-HA-WPRE) induced the highest level of protective immunity, such that immunization with 10-fold lower DNA doses prevented death in 100% of the mice upon lethal viral challenge, whereas all mice immunized with the conventional pCMV-HA vaccine succumbed to influenza infection.

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Section: Discussionmentioning

confidence: 99%

The Hybrid Cytomegalovirus Enhancer/Chicken β-Actin Promoter along with Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element Enhances the Protective Efficacy of DNA Vaccines

Garg

Oran

Hon

et al. 2004

The Journal of Immunology

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“…This immunization system can elicit cellular and humoral immune responses which mimic those to live attenuated virus vaccines while avoiding some of the possible problems associated with live vaccines. Gene gun vaccination is a safe and inexpensive procedure which has been shown to be effective against various pathogens including HBV (11,30,(50)(51)(52)(53). In the present work, we have investigated the effects of gene gun immunization with WHcAg to elicit T-cell immunity.…”

mentioning

confidence: 99%

Protection against Woodchuck Hepatitis Virus (WHV) Infection by Gene Gun Coimmunization with WHV Core and Interleukin-12

Garcia-Navarro

Blanco-Urgoiti

Berraondo

et al. 2001

J Virol

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Woodchuck hepatitis virus (WHV) and hepatitis B virus (HBVHepatitis B virus (HBV) is a partially double-stranded DNA virus encoding envelope (pre-S1, pre-S2, HBsAg), nucleocapsid (HBcAg, HBeAg), trans-activating (X), and polymerase (Pol) proteins (46). Clinical manifestations of HBV infection range from acute and chronic hepatitis to cirrhosis and hepatocellular carcinoma in humans (6). There are more than 350 million chronic HBV carriers worldwide (54), and HBV is an important cause of morbidity and mortality in the Third World.Several reports have shown that the immune response plays a significant role in both HBV clearance and pathogenesis of hepatitis B (13). A vigorous polyclonal and multispecific cellular response to HBV has been associated with recovery from acute infection. Cytotoxic T lymphocytes (CTLs) and T-helper (Th) cells with specificity for HBcAg and most HBV proteins can be detected in the circulation during acute infection (22,34,37). In contrast, defective CTL and Th cell responses are observed in chronic HBV carriers, except during exacerbation (48). As has been reported for several viral infections, a pref-

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“…Cellular responses are very important in clearing influenza A virus infections in mice (7,27). In our experiment, reduced viral clearance from lungs of pNP-immunized diabetic mice in comparison to healthy mice may be due to suppression of the cytotoxic responses.…”

Section: Discussionmentioning

confidence: 56%

“…Vaccines employing recombinant-DNA technologies are an alternative to inactivated virus and live attenuated virus vaccines (4,10). Many influenza DNA vaccine experiments have successfully demonstrated that DNA vaccines are effective for the induction of immune responses against the influenza virus (5,7,8,27).…”

mentioning

confidence: 99%

A DNA Vaccine-Encoded Nucleoprotein of Influenza Virus Fails To Induce Cellular Immune Responses in a Diabetic Mouse Model

Jamali

Sabahi

Bamdad

et al. 2010

Clin Vaccine Immunol

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Influenza virus infections cause yearly epidemics and are a major cause of lower respiratory tract illnesses in humans worldwide. Influenza virus has long been recognized to be associated with higher morbidity and mortality in diabetic patients. Vaccination is an effective tool to prevent influenza virus infection in this group of patients. Vaccines employing recombinant-DNA technologies are an alternative to inactivated virus and live attenuated virus vaccines. Internal highly conserved viral nucleoprotein (NP) can be delivered as a DNA vaccine to provide heterosubtypic immunity, offering resistance against various influenza virus strains. In this study, we investigated the efficacy of an NP DNA vaccine for induction of cell-mediated immune responses and protection against influenza virus infection in a mouse model of diabetes. Healthy and diabetic BALB/c mice were immunized on days 0, 14, and 28 by injection of NP DNA vaccine. Two weeks after the last immunization, the cellular immune response was evaluated by gamma interferon (IFN-␥), lymphocyte proliferation, and cytotoxicity assays. The mice were challenged with influenza virus, and the viral titers in the lungs were measured on day 4. Diabetic mice showed significantly smaller amounts of IFN-␥ production, lymphocyte proliferation, and cytotoxicity responses than nondiabetic mice. Furthermore, higher titers of the influenza virus were detected after challenge in the lungs of the diabetic mice. The present data suggest that the NP DNA vaccine with the protocol of immunization described here is not able to induce efficient cellular immune responses against influenza virus infection in diabetic mice.

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Protective immunity by intramuscular injection of low doses of influenza virus DNA vaccines

Cited by 161 publications

References 11 publications

The Hybrid Cytomegalovirus Enhancer/Chicken β-Actin Promoter along with Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element Enhances the Protective Efficacy of DNA Vaccines

The Hybrid Cytomegalovirus Enhancer/Chicken β-Actin Promoter along with Woodchuck Hepatitis Virus Posttranscriptional Regulatory Element Enhances the Protective Efficacy of DNA Vaccines

Protection against Woodchuck Hepatitis Virus (WHV) Infection by Gene Gun Coimmunization with WHV Core and Interleukin-12

A DNA Vaccine-Encoded Nucleoprotein of Influenza Virus Fails To Induce Cellular Immune Responses in a Diabetic Mouse Model

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