Protective Efficacy against Respiratory Syncytial Virus following Murine Neonatal Immunization with BBG2Na Vaccine: Influence of Adjuvants and Maternal Antibodies

Siegrist, Claire‐Anne; Plotnicky-Gilquin, Hélène; Córdova, Marco; Berney, Monika; Bonnefoy, Jean‐Yves; Nguyen, Thien Ngoc; Lambert, Paul‐Henri; Power, Ultan F.

doi:10.1086/314778

Cited by 66 publications

(39 citation statements)

References 41 publications

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“…In addition, the ability of RSV to evade immune responses in humans should continue to be investigated. We are suggesting that particular attention should be given to the development of candidate HRSV subunit vaccines including only the central region of the G protein (62). Considering the mutations in this region described here, this subunit-vaccine approach should be used with caution.…”

Section: Discussionmentioning

confidence: 97%

Evolution of Bovine Respiratory Syncytial Virus

Valarcher

Schelcher

Bourhy

2000

J Virol

164

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Until now, the analysis of the genetic diversity of bovine respiratory syncytial virus (BRSV) has been based on small numbers of field isolates. In this report, we determined the nucleotide and deduced amino acid sequences of regions of the nucleoprotein (N protein), fusion protein (F protein), and glycoprotein (G protein) of 54 European and North American isolates and compared them with the sequences of 33 isolates of BRSV obtained from the databases, together with those of 2 human respiratory syncytial viruses and 1 ovine respiratory syncytial virus. A clustering of BRSV sequences according to geographical origin was observed. We also set out to show that a continuous evolution of the sequences of the N, G, and F proteins of BRSV has been occurring in isolates since 1967 in countries where vaccination was widely used. The exertion of a strong positive selective pressure on the mucin-like region of the G protein and on particular sites of the N and F proteins is also demonstrated. Furthermore, mutations which are located in the conserved central hydrophobic part of the ectodomain of the G protein and which result in the loss of four Cys residues and in the suppression of two disulfide bridges and an ␣ helix critical to the three-dimensional structure of the G protein have been detected in some recent French BRSV isolates. This conserved central region, which is immunodominant in BRSV G protein, thus has been modified in recent isolates. This work demonstrates that the evolution of BRSV should be taken into account in the rational development of future vaccines. (38,39,40,49). These two related viruses share common epidemiological, clinical, and pathological characteristics. The respiratory syncytial viruses (RSV) are the most common and important cause of lower respiratory tract illness in cattle and young infants (71). More than 70% of calves exhibit a positive serological response against BRSV by the age of 12 months. Bovine respiratory syncytial virus (BRSV) and human respiratory syncytial virus (HRSV) are members of the genus Pneumovirus, subfamily Pneumovirinae, and family ParamyxoviridaeNeutralization tests (9) and reaction patterns with specific monoclonal antibodies (2, 48) have revealed that HRSV contains two major groups, A and B. The main differences between these two groups are located in the glycoprotein (G protein), while others are located in the fusion protein (F protein) and nucleoprotein (N protein) (48, 51). Subgroups within the G and F proteins of BRSV have been characterized more recently by serological analysis of a limited number of isolates and confirmed by phylogenetic analysis (20,54,60). Further studies of BRSV variability have focused on the G protein, which was shown to be the most variable protein and, with the F protein, one of the targets for neutralizing antibodies. A low percentage of sequence divergence between and within the G proteins of BRSV subgroups has been reported, suggesting that BRSV has the same extent of diversity as HRSV (15,21,36,44,66).The G protein is responsib...

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Section: Discussionmentioning

confidence: 97%

Evolution of Bovine Respiratory Syncytial Virus

Valarcher

Schelcher

Bourhy

2000

J Virol

164

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“…However, it has been demonstrated that significant IgG responses may be induced after immunization with protein antigens (reviewed in [23]), indicating that T cell help to promote isotype switch of B cells from IgM to IgG is present already in the neonatal period of life. The IgG subclass pattern observed after early life immunization of mice is, nevertheless, characterized by a relatively high IgG1/IgG2a ratio [29,30]. This pattern reflects the Th2-biased conditions of the immune system in the newborn, shown by low production of IFN-c, but relatively high production of IL-4, IL-5 and IL-13 after immunization with TD antigens under neutral conditions [30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

et al. 2006

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Immunization with a tetanus-protein (TT) pneumococcal polysaccharide (PPS) conjugate vaccine (Pnc1-TT) induces protective immunity against lethal pneumococcal infections in neonatal and infant mice, but anti-PPS IgG response and protective efficacy is lower than in adult mice. Here, we show that reduced antibody (Ab) response and protection against infections is directly related to impaired T cell response to the carrier. Whereas spleen cells from adult mice immunized with Pnc1-TT responded with proliferation and IFN-gamma secretion to in vitro stimulation with TT, spleen cells from neonatal and infant mice did not. However, significant, but age dependent, Th2-cytokine responses were observed in mice immunized with Pnc1-TT. Impaired IFN-gamma production upon TT-stimulation in vitro was also reflected in reduced IFN-gamma/IL-5 ratio. The IL--5 response correlated with IgG anti-PPS titers, and the lack of PPS Ab in the majority of neonatal mice was clearly associated with absence of carrier-specific IL-5 production. These results show that immunization with Pnc1-TT induces carrier-specific T cell responses that increase with age and determine the levels of PPS-specific Ab elicited. Whereas a weak and Th2-biased response was observed in neonatal mice, infant mice showed a mixed Th1-Th2 response as observed in adults

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“…Thus, the development of RSV vaccines has long been a priority for infants and young children (2, 6 -9), and more recently, vaccines are being developed for older children at risk for serious complications of infection and for the elderly (10 -12). RSV vaccine development has been focused toward live temperature-sensitive, attenuated vaccines and subunit vaccines based on the F and/or G glycoproteins (13,14). In animal model systems the F glycoprotein is the most effective, and G glycoprotein is the next most effective in inducing neutralizing Abs and protective immunity, but vaccination with the G glycoprotein generally induces only limited protection (15,16).…”

mentioning

confidence: 99%

CD40 Ligand (CD154) Enhances the Th1 and Antibody Responses to Respiratory Syncytial Virus in the BALB/c Mouse

Tripp

Jones

Anderson

et al. 2000

The Journal of Immunology

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CD40 ligand (CD40L) is a cell surface costimulatory molecule expressed mainly by activated T cells. CD40L is critically important for T-B cell and T cell-dendritic cell interactions. CD40L expression promotes Th1 cytokine responses to protein Ags and is responsible for Ig isotype switching in B cells. Respiratory syncytial virus (RSV) is an important pathogen of young children and the elderly, which causes bronchiolitis and pneumonia. Studies of mice infected with RSV suggest that a Th2 cytokine response may be responsible for enhanced pulmonary disease. To investigate the effect CD40L has on RSV immunity, mice were infected simultaneously with RSV and either an empty control adenovirus vector or one expressing CD40L or were coimmunized with plasmid DNA vectors expressing CD40L and RSV F and/or G proteins and subsequently challenged with RSV. The kinetics of the intracellular and secreted cytokine responses, the cytotoxic T lymphocyte precursor frequency, NO levels in lung lavage, rates of virus clearance, and anti-RSV Ab titers were determined. These studies show that coincident expression of CD40L enhances the Th1 (IL-2 and IFN-γ) cytokine responses, increases the expression of TNF-α and NO, accelerates virus clearance, and increases the anti-F and anti-G Ab responses. These data suggest that CD40L may have the adjuvant properties needed to optimize the safety and efficacy of RSV vaccines.

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Protective Efficacy against Respiratory Syncytial Virus following Murine Neonatal Immunization with BBG2Na Vaccine: Influence of Adjuvants and Maternal Antibodies

Cited by 66 publications

References 41 publications

Evolution of Bovine Respiratory Syncytial Virus

Evolution of Bovine Respiratory Syncytial Virus

Early life T cell responses to pneumococcal conjugates increase with age and determine the polysaccharide‐specific antibody response and protective efficacy

CD40 Ligand (CD154) Enhances the Th1 and Antibody Responses to Respiratory Syncytial Virus in the BALB/c Mouse

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