Immunoprotective Activity and Safety of a RespiratorySyncytial Virus Vaccine: Mucosal Delivery of Fusion Glycoprotein with aCpG OligodeoxynucleotideAdjuvant

Prince, Gregory A.; Mond, James J.; Porter, David D.; Yim, Kevin C.; Lan, Steve J.; Klinman, Dennis M.

doi:10.1128/jvi.77.24.13156-13160.2003

Cited by 50 publications

(37 citation statements)

References 29 publications

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“…This group also demonstrated the largest reduction in median viral RNA copy number. This agrees with an earlier report in which intranasal immunization of cotton rats with RSV F protein plus CpG ODN reduced viral production upon challenge (Prince et al, 2003). They, however, required amounts of purified antigen and/or CpG ODN higher than those used in Because of their ability to form non-covalent complexes with antigens and other adjuvants, PP are attractive for use in mucosal immunization, a situation in which constant secretion of mucous membrane fluids and high turnover of epithelial cells threaten the stability and uptake of vaccine components.…”

Section: Discussionsupporting

confidence: 82%

“…Several intranasal-immunization strategies have been employed to protect rodents from RSV challenge, including recombinant F protein adjuvanted with CpG ODN (Prince et al, 2003), cholera toxin (Tebbey et al, 2000;Walsh, 1993) or caprylic/capric glycerides and polyoxyethylene-20-sorbitan monolaurate (Tebbey et al, 1999), as well as live viral (Kahn et al, 2001;Matsuoka et al, 2002;Stott et al, 1987) or bacterial (Cano et al, 2000;Falcone et al, 2006) vectors expressing whole RSV proteins or peptides. One of the challenges of intranasal immunization is delivering the vaccine components in such a manner that they are not degraded or flushed out prior to the initiation of the immune response.…”

Section: Introductionmentioning

confidence: 99%

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Intranasal immunization of mice with a formalin-inactivated bovine respiratory syncytial virus vaccine co-formulated with CpG oligodeoxynucleotides and polyphosphazenes results in enhanced protection

Mapletoft

Oumouna

Kovacs-Nolan

et al. 2008

Journal of General Virology

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As respiratory syncytial virus (RSV) targets the mucosal surfaces of the respiratory tract, induction of both systemic and mucosal immunity will be critical for optimal protection. In this study, the ability of an intranasally delivered, formalin-inactivated bovine RSV (FI-BRSV) vaccine co-formulated with CpG oligodeoxynucleotides (ODN) and polyphosphazenes (PP) to induce systemic and mucosal immunity, as well as protection from BRSV challenge, was evaluated. Intranasal immunization of mice with FI-BRSV formulated with CpG ODN and PP resulted in both humoral and cell-mediated immunity, characterized by enhanced production of BRSV-specific serum IgG, as well as increased gamma interferon and decreased interleukin-5 production by in vitro-restimulated splenocytes. These mice also developed mucosal immune responses, as was evident from increased production of BRSV-specific IgG and IgA in lung-fragment cultures. Indeed, the increases in serum and mucosal IgG, and in particular mucosal IgA and virusneutralizing antibodies, were the most critical differences observed between FI-BRSV formulated with both CpG ODN and PP in comparison to formulations with CpG ODN, non-CpG ODN or PP individually. Finally, FI-BRSV/CpG/PP was the only formulation that resulted in a significant reduction in viral replication upon BRSV challenge. Co-formulation of CpG ODN and PP is a promising new vaccine platform technology that may have applications in mucosal immunization in humans. INTRODUCTIONHuman respiratory syncytial virus (HRSV) is a leading cause of respiratory disease in infants and young children worldwide (Heilman, 1990) and is responsible for significant economic loss; in the year 2000 alone, there were 86 000 HRSV infection-related hospitalizations in the USA, costing a total of $394 000 000 (Paramore et al., 2004). Nearly 98 % of these hospitalizations occurred in children under 5 years old. Between 1997 and 2000, HRSV bronchiolitis was the leading cause of infant hospitalization and, in 1999, an estimated 360 HRSV-associated postneonatal deaths (i.e. in children aged between 28 days and 1 year) occurred in the USA (Leader & Kohlhase, 2003).Like HRSV, bovine respiratory syncytial virus (BRSV) is an enveloped, non-segmented, single-stranded RNA pneumovirus of the family Paramyxoviridae and order Mononegavirales. BRSV is responsible for significant economic loss to the cattle industry (Stott & Taylor, 1985) and is one of the four known viral components of bovine shipping fever. HRSV and BRSV have similar clinical outcomes in their respective host species, ranging from asymptomatic infection to bronchiolitis and pneumonia, and sometimes death (Philippou et al., 2000). The distribution of both viruses is worldwide.Whilst there are several commercial BRSV vaccines currently available for immunizing cattle, better vaccines that are more efficacious in the face of maternal antibodies and that induce longer-lasting protection would be desirable. Also, there is currently no safe and effective vaccine against HRSV available for use in h...

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Intranasal immunization of mice with a formalin-inactivated bovine respiratory syncytial virus vaccine co-formulated with CpG oligodeoxynucleotides and polyphosphazenes results in enhanced protection

Mapletoft

Oumouna

Kovacs-Nolan

et al. 2008

Journal of General Virology

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show abstract

“…This adjuvant also had a dramatic effect in reducing both Th-1 and Th-2-type cytokines in a model of FI-RSV vaccine enhancement in cotton rats [4]. Enhancement was also noted when a purified hRSV F protein was used as a vaccine together with a CpG oligodeoxynucleotide adjuvant [21]. We believe that all Paramyxoviridae probably have the tendency to cause vaccine enhancement when nonreplicating vaccines are used.…”

Section: Discussionmentioning

confidence: 78%

“…Recent studies indicate that infection of cotton rats with hMPV is associated with efficient viral replication in the lung and reproducible pulmonary pathology [10,28,30]. The cotton rat has also been used extensively to study hRSV especially in the area of enhanced pulmonary disease caused by some vaccine candidates for hRSV [19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

Human metapneumovirus: Enhanced pulmonary disease in cotton rats immunized with formalin-inactivated virus vaccine and challenged

Yim¹,

Cragin²,

Boukhvalova³

et al. 2007

Vaccine

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Cotton rats (Sigmodon hispidus) are susceptible to the recently discovered human metapneumovirus (hMPV), an agent closely related to human respiratory syncytial virus. Since certain respiratory syncytial virus vaccines can induce enhanced disease upon viral challenge, we have done similar experiments with hMPV in cotton rats. Young adult cotton rats were vaccinated with a formalininactivated preparation of hMPV strain C-85473, or with a mock preparation of the vaccine on day 0 and again on day 28. All animals were challenged intranasally on day 49 with 10 7 TCID 50 of the same hMPV strain. Animals were sacrificed on days 4, 7, and 10 post-challenge and lungs were removed for viral quantitation, histopathology, and cytokine mRNA expression analysis (interferongamma (IFN-γ) and interleukin-4 (IL-4)). Although the vaccinated animals showed almost complete protection from viral replication in the lungs (<10 2.0 TCID 50 per gram), there was a dramatic increase in the lung pathology, particularly the interstitial pneumonitis and alveolitis with elevated serum neutralizing antibody titer prior to challenge. Cytokine profiles were distinctive from those observed during primary infection and re-infection. The data raise safety concerns for hMPV vaccine preparations.

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“…Patients are infected by H. pylori mostly in their childhood, therefore, the protective therapy by vaccine is more suitable than antibiotic therapy. Intranasal immunization has been gaining attention as a potential approach for the development of vaccines that prevent and treat infectious diseases in the respiratory tract 30 ). The characterization and the mechanism of the immune· cells in the nasal and gastrointestinal mucosa are not fully investigated.…”

Section: Discussionmentioning

confidence: 99%

EFFECTIVENESS OF INTRAGASTRIC IMMUNIZATION WITH PROTEIN AND OLIGODEOXYNUCLEOTIDES CONTAINING A CpG MOTIF FOR INDUCING A GASTROINTESTINAL MUCOSAL IMMUNE RESPONSE IN MICE

Hikichi

Kobayashi

Oyama

et al. 2005

FJMS

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Immunoprotective Activity and Safety of a RespiratorySyncytial Virus Vaccine: Mucosal Delivery of Fusion Glycoprotein with aCpG OligodeoxynucleotideAdjuvant

Cited by 50 publications

References 29 publications

Intranasal immunization of mice with a formalin-inactivated bovine respiratory syncytial virus vaccine co-formulated with CpG oligodeoxynucleotides and polyphosphazenes results in enhanced protection

Intranasal immunization of mice with a formalin-inactivated bovine respiratory syncytial virus vaccine co-formulated with CpG oligodeoxynucleotides and polyphosphazenes results in enhanced protection

Human metapneumovirus: Enhanced pulmonary disease in cotton rats immunized with formalin-inactivated virus vaccine and challenged

EFFECTIVENESS OF INTRAGASTRIC IMMUNIZATION WITH PROTEIN AND OLIGODEOXYNUCLEOTIDES CONTAINING A CpG MOTIF FOR INDUCING A GASTROINTESTINAL MUCOSAL IMMUNE RESPONSE IN MICE

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