Immunogenicity and efficacy of codon optimized DNA vaccines encoding the F-protein of respiratory syncytial virus

Ternette, Nicola; Tippler, Bettina; Überla, Klaus; Grünwald, Thomas

doi:10.1016/j.vaccine.2007.07.025

Cited by 70 publications

(65 citation statements)

References 38 publications

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“…Mice in the control groups received the AdV-OVA control or were left untreated (not immunized). Mice were challenged intranasally 3 weeks after the last immunization under Ketamine/Xylazine anesthesia (as described above) with 10 7 PFU of RSV strain Long in 50 l PBS as described previously (52). Five days after infection, mice were sacrificed, and bronchoalveolar lavage fluids (BALs) were collected from lungs by applying and removing 1 ml PBS twice.…”

Section: Methodsmentioning

confidence: 99%

“…Stocks of the RSV Long strain were prepared as described previously by infection of HEp2 cells at a low multiplicity of infection (52). Defective interfering particles from our stock were removed by two subsequent limiting dilution steps as described previously (17).…”

Section: Methodsmentioning

confidence: 99%

“…Besides being a target for neutralizing antibodies, RSV F additionally contains cytotoxic-T-cell epitopes (1,37). Moreover, RSV F based DNA vaccines induced encouraging immune responses of a balanced Th1/Th2 type in mice, as pulmonary eosinophilia and disease-enhancing effects were not observed after viral challenge (4,5,19,31,52). Additionally, RSV F is highly conserved between the two antigenic subgroups of RSV, which allows generation of cross-reactive antibodies after immunization (26).…”

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confidence: 99%

“…We recently showed that vaccination with codon-optimized RSV F expression plasmids induced improved humoral immune responses in mice compared to vaccination with wildtype cDNA expression plasmids (52). Consequently, viral load was reduced 13-fold in mice immunized with full-length RSV F and 170-fold in mice immunized with the soluble form of RSV F following RSV challenge in comparison to nonimmunized mice.…”

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confidence: 99%

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Protective Efficacy and Immunogenicity of an Adenoviral Vector Vaccine Encoding the Codon-Optimized F Protein of Respiratory Syncytial Virus

Kohlmann

Schwannecke

Tippler

et al. 2009

J Virol

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Adenoviral vectors (AdV) have received considerable attention for vaccine development because of their high immunogenicity and efficacy. In previous studies, it was shown that DNA immunization of mice with codonoptimized expression plasmids encoding the fusion protein of respiratory syncytial virus (RSV F) resulted in enhanced protection against RSV challenge compared to immunization with plasmids carrying the wild-type cDNA sequence of RSV F. In this study, we constructed AdV carrying the codon-optimized full-length RSV F gene (AdV-F) or the soluble form of the RSV F gene (AdV-Fsol). BALB/c mice were immunized twice with AdV-F or AdV-Fsol and challenged with RSV intranasally. Substantial levels of antibody to RSV F were induced by both AdV vaccines, with peak neutralizing-antibody titers of 1:900. Consistently, the viral loads in lung homogenates and bronchoalveolar lavage fluids were significantly reduced by a factor of more than 60,000. The protection against viral challenge could be measured even 8 months after the booster immunization. AdV-F and AdV-Fsol induced similar levels of immunogenicity and protective efficacy. Therefore, these results encourage further development of AdV vaccines against RSV infection in humans.Human respiratory syncytial virus (RSV) is a highly infectious member of the paramyxovirus family causing upper and lower respiratory tract infections in humans. Serious acute RSV infections, including fatal cases of bronchiolitis and pneumonia, occur particularly in premature infants, immunocompromised adults, and patients with pre-existing chronic lung diseases or underlying heart defects (11,12,14,39,46,56). In young children, RSV is the most common respiratory tract pathogen, accounting for approximately 50% of hospitalizations due to lower respiratory tract infections (21). In population-based surveillance studies for hospitalization in Europe, RSV was identified in 42 to 45% of enrolled children younger than 2 years with lower respiratory tract infections, and the rate of hospitalization due to RSV-induced respiratory illnesses was estimated at 3 to 6% among industrialized nations (45). Children with severe RSV infections suffer from oxygen deficiency with cyanosis and require intensive medical care. Furthermore, RSV infection in childhood is suspected to be a risk factor for development of asthma (36,41,43,59). The urgent need for an RSV vaccine is further demonstrated by a study showing that levels of disease burden, mortality, and morbidity caused by RSV infections in the elderly are comparable to those induced by nonpandemic influenza A infections (11). However, the immunization of children with a formalininactivated (FI) RSV vaccine in the 1960s resulted in a more severe clinical illness, with two fatal cases, than in nonvaccinated infants following RSV infection, pointing out the difficulties in developing a safe and efficacious RSV vaccine (7,29). It was shown previously that the enhanced disease severity and the development of pulmonary eosinophilia are mainly attributable to a...

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Protective Efficacy and Immunogenicity of an Adenoviral Vector Vaccine Encoding the Codon-Optimized F Protein of Respiratory Syncytial Virus

Kohlmann

Schwannecke

Tippler

et al. 2009

J Virol

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“…DNA vaccines are immunogenic and effective in protection against several viral infections, including HRSV. 21,25,26,31 HRSV DNA vaccine candidates that used commercially available plasmid vectors such as pcDNA3.1, 23,32 pET-32, 33 and pVCL1012 34 have variable immunogenicity and the ability to confront virus challenge. A novel immunization vector, which is currently unavailable in the market, was constructed to induce a potent CTL response and tumor regression in mice with cervical cancer 35 or prostate carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Novel recombinant DNA vaccine candidates for human respiratory syncytial virus: Preclinical evaluation of immunogenicity and protection efficiency

Farrag

Amer

Öhlschläger

et al. 2017

Human Vaccines & Immunotherapeutics

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The development of safe and potent vaccines for human respiratory syncytial virus (HRSV) is still a challenge for researchers worldwide. DNA-based immunization is currently a promising approach that has been used to generate human vaccines for different age groups. In this study, novel HRSV DNA vaccine candidates were generated and preclinically tested in BALB/c mice. Three different versions of the codonoptimized HRSV fusion (F) gene were individually cloned into the pPOE vector. The new recombinant vectors either express full-length (pPOE-F), secretory (pPOE-TF), or M2 82-90 linked (pPOE-FM2) forms of the F protein. Distinctive expression of the F protein was identified in HEp-2 cells transfected with the different recombinant vectors using ELISA and immunofluorescence. Mice immunization verified the potential for recombinant vectors to elicit significant levels of neutralizing antibodies and CD8 C T-cell lymphocytes. pPOE-TF showed higher levels of gene expression in cell culture and better induction of the humoral and cellular immune responses. Following virus challenge, mice that had been immunized with the recombinant vectors were able to control virus replication and displayed lower inflammation compared with mice immunized with empty pPOE vector or formalin-inactivated HRSV vaccine. Moreover, pulmonary cytokine profiles of mice immunized with the 3 recombinant vectors were similar to those of the mock infected group. In conclusion, recombinant pPOE vectors are promising HRSV vaccine candidates in terms of their safety, immunogenicity and protective efficiency. These data encourage further evaluation in phase I clinical trials.

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DNA Plasmids for Non‐viral Gene Therapy of Cancer

Najjar

Moyes

Cooper

2014

Cancer Gene Therapy by Viral and Non‐viral Vectors

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Immunogenicity and efficacy of codon optimized DNA vaccines encoding the F-protein of respiratory syncytial virus

Cited by 70 publications

References 38 publications

Protective Efficacy and Immunogenicity of an Adenoviral Vector Vaccine Encoding the Codon-Optimized F Protein of Respiratory Syncytial Virus

Protective Efficacy and Immunogenicity of an Adenoviral Vector Vaccine Encoding the Codon-Optimized F Protein of Respiratory Syncytial Virus

Novel recombinant DNA vaccine candidates for human respiratory syncytial virus: Preclinical evaluation of immunogenicity and protection efficiency

DNA Plasmids for Non‐viral Gene Therapy of Cancer

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