Immunogenicity of RSV F DNA Vaccine in BALB/c Mice

Eroğlu, Erdal; Singh, Shree R.; Bawage, Swapnil; Tiwari, Pooja; Vig, Komal; Pillai, Shreekumar R.; Dennis, Vida A.

doi:10.1155/2016/7971847

Cited by 7 publications

(5 citation statements)

References 35 publications

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“…To our knowledge, this is the first report studying the impact of loss of individual N-glycosylation sites of the hRSV F protein on antibody responses by immunization of BALB/c mice with plasmids encoding RSV F glycomutants. Previous research already showed the potential of RSV F DNA immunization in mice to induce in vitro neutralizing antibody responses [ 50 , 51 , 52 , 53 ] which was also obtained in our approach using codon-optimized RSV F sequences. Based on the antibody titres after two subsequent immunizations, a role of N-glycosylation at position N70 in the induction of neutralizing antibody responses could be suggested.…”

Section: Discussionmentioning

confidence: 57%

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Removal of the N-Glycosylation Sequon at Position N116 Located in p27 of the Respiratory Syncytial Virus Fusion Protein Elicits Enhanced Antibody Responses after DNA Immunization

Leemans

Boeren

Gucht

et al. 2018

Viruses

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Prevention of severe lower respiratory tract infections in infants caused by the human respiratory syncytial virus (hRSV) remains a major public health priority. Currently, the major focus of vaccine development relies on the RSV fusion (F) protein since it is the main target protein for neutralizing antibodies induced by natural infection. The protein conserves 5 N-glycosylation sites, two of which are located in the F2 subunit (N27 and N70), one in the F1 subunit (N500) and two in the p27 peptide (N116 and N126). To study the influence of the loss of one or more N-glycosylation sites on RSV F immunogenicity, BALB/c mice were immunized with plasmids encoding RSV F glycomutants. In comparison with F WT DNA immunized mice, higher neutralizing titres were observed following immunization with F N116Q. Moreover, RSV A2-K-line19F challenge of mice that had been immunized with mutant F N116Q DNA was associated with lower RSV RNA levels compared with those in challenged WT F DNA immunized animals. Since p27 is assumed to be post-translationally released after cleavage and thus not present on the mature RSV F protein, it remains to be elucidated how deletion of this glycan can contribute to enhanced antibody responses and protection upon challenge. These findings provide new insights to improve the immunogenicity of RSV F in potential vaccine candidates.

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Section: Discussionmentioning

confidence: 57%

“…Proteolysis to form peptides or glycopeptides and recognition of T cell receptors by MHC molecules can be affected by glycans positioned near proteolytic sites [ 65 ]. Additionally, previous immunization experiments showed upregulation of Th1 cell responses after immunization of mice with a full-length RSV F DNA vaccine [ 51 , 52 ].…”

Section: Discussionmentioning

confidence: 99%

Removal of the N-Glycosylation Sequon at Position N116 Located in p27 of the Respiratory Syncytial Virus Fusion Protein Elicits Enhanced Antibody Responses after DNA Immunization

Leemans

Boeren

Gucht

et al. 2018

Viruses

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“…158 Recent preclinical results exhibit effective neutralization of RSV. [159][160][161][162][163] The most advanced of these is the Novavax F-protein VLP nanoparticle vaccine with aluminum hydroxide adjuvant, which is in phase III for maternal vaccination. 129,130 Transplacental transmission of neutralizing antibodies has been demonstrated in preclinical studies, although this has not conferred significant protection from RSV.…”

Section: Vaccines and Mabsmentioning

confidence: 99%

Promising approaches for the treatment and prevention of viral respiratory illnesses

Papadopoulos

Megremis

Kitsioulis

et al. 2017

Journal of Allergy and Clinical Immunology

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Viral respiratory tract infections are the most common human ailments, leading to enormous health and economic burden. Hundreds of viral species and subtypes have been associated with these conditions, with influenza viruses, respiratory syncytial virus, and rhinoviruses being the most frequent and with the highest burden. When considering prevention or treatment of viral respiratory tract infections, potential targets include the causative pathogens themselves but also the immune response, disease transmission, or even just the symptoms. Strategies targeting all these aspects are developing concurrently, and several novel and promising approaches are emerging. In this perspective we overview the entire range of options and highlight some of the most promising approaches, including new antiviral agents, symptomatic or immunomodulatory drugs, the re-emergence of natural remedies, and vaccines and public health policies toward prevention. Wide-scale prevention through immunization appears to be within reach for respiratory syncytial virus and promising for influenza virus, whereas additional effort is needed in regard to rhinovirus, as well as other respiratory tract viruses.

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“…Immunization of mice with pSinCCHF-52S construct elicited CCHFV NP-specific IgG antibodies. CCHFV specific antibodies were of predominantly IgG2a subclass; the high IgG2a/IgGa and IgG2a/IgG2b ratios spoke of a predominantly Th1-type immune response [48,49]. The Th-1 immune response was also supported by strong correlations between anti-CCHFV NP IgG2a and CCHFV NP-specific IFN-γ and IL-2 production.…”

Section: Discussionmentioning

confidence: 92%

Immunogenicity of a DNA-Based Sindbis Replicon Expressing Crimean–Congo Hemorrhagic Fever Virus Nucleoprotein

2021

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Crimean–Congo hemorrhagic fever virus (CCHFV) infrequently causes hemorrhagic fever in humans with a case fatality rate of 30%. Currently, there is neither an internationally approved antiviral drug nor a vaccine against the virus. A replicon based on the Sindbis virus vector encoding the complete open reading frame of a CCHFV nucleoprotein from a South African isolate was prepared and investigated as a possible candidate vaccine. The transcription of CCHFV RNA and recombinant protein production by the replicon were characterized in transfected baby hamster kidney cells. A replicon encoding CCHFV nucleoprotein inserted in plasmid DNA, pSinCCHF-52S, directed transcription of CCHFV RNA in the transfected cells. NIH-III heterozygous mice immunized with pSinCCHF-52S generated CCHFV IgG specific antibodies with notably higher levels of IgG2a compared to IgG1. Splenocytes from mice immunized with pSinCCHF-52S secreted IFN-γ and IL-2, low levels of IL-6 or IL-10, and no IL-4. No specific cytokine production was registered in splenocytes of mock-immunized mice (p < 0.05). Thus, our study demonstrated the expression of CCHFV nucleoprotein by a Sindbis virus vector and its immunogenicity in mice. The spectrum of cytokine production and antibody profile indicated predominantly Th1-type of an anti-CCHFV immune response. Further studies in CCHFV-susceptible animals are necessary to determine whether the induced immune response is protective.

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Immunogenicity of RSV F DNA Vaccine in BALB/c Mice

Cited by 7 publications

References 35 publications

Removal of the N-Glycosylation Sequon at Position N116 Located in p27 of the Respiratory Syncytial Virus Fusion Protein Elicits Enhanced Antibody Responses after DNA Immunization

Removal of the N-Glycosylation Sequon at Position N116 Located in p27 of the Respiratory Syncytial Virus Fusion Protein Elicits Enhanced Antibody Responses after DNA Immunization

Promising approaches for the treatment and prevention of viral respiratory illnesses

Immunogenicity of a DNA-Based Sindbis Replicon Expressing Crimean–Congo Hemorrhagic Fever Virus Nucleoprotein

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