Adjuvants influence the quantitative and qualitative immune response in BALBc mice immunized with respiratory syncytial virus FG subunit vaccine

Neuzil, Kathleen M.; Johnson, Joyce E.; Tang, Yi‐Wei; Prieels, Jean‐Paul; Slaoui, Moncef; Gar, Natalie S.; Graham, Barney S.

doi:10.1016/s0264-410x(97)00218-1

Cited by 67 publications

(49 citation statements)

References 29 publications

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“…Mouse models of FI-RSV vaccine-enhanced disease have shown that pulmonary eosinophilia is a hallmark of disease and is linked to prominent production of Th2 cytokines, including interleukin 4 (IL-4), IL-5, and IL-13 (13)(14)(15)(16). IL-4 and IL-5 play major roles in pathogenesis in the mouse models of FI-RSV vac-RNI assay.…”

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confidence: 99%

Dual Proinflammatory and Antiviral Properties of Pulmonary Eosinophils in Respiratory Syncytial Virus Vaccine-Enhanced Disease

Townsend

Herrero

et al. 2015

J Virol

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Human respiratory syncytial virus (RSV) is a major cause of morbidity and severe lower respiratory tract disease in the elderly and very young, with some infants developing bronchiolitis, recurrent wheezing, and asthma following infection. Previous studies in humans and animal models have shown that vaccination with formalin-inactivated RSV (FI-RSV) leads to prominent airway eosinophilic inflammation following RSV challenge; however, the roles of pulmonary eosinophilia in the antiviral response and in disease pathogenesis are inadequately understood. In vivo studies in mice with eotaxin and/or interleukin 5 (IL-5) deficiency showed that FI-RSV vaccination did not lead to enhanced pulmonary disease, where following challenge there were reduced pulmonary eosinophilia, inflammation, Th2-type cytokine responses, and altered chemokine (TARC and CCL17) responses. In contrast to wild-type mice, RSV was recovered at high titers from the lungs of eotaxin-and/or IL-5-deficient mice. Adoptive transfer of eosinophils to FI-RSV-immunized eotaxin-and IL-5-deficient (double-deficient) mice challenged with RSV was associated with potent viral clearance that was mediated at least partly through nitric oxide. These studies show that pulmonary eosinophilia has dual outcomes: one linked to RSV-induced airway inflammation and pulmonary pathology and one with innate features that contribute to a reduction in the viral load. IMPORTANCEThis study is critical to understanding the mechanisms attributable to RSV vaccine-enhanced disease. This study addresses the hypothesis that IL-5 and eotaxin are critical in pulmonary eosinophil response related to FI-RSV vaccine-enhanced disease. The findings suggest that in addition to mediating tissue pathology, eosinophils within a Th2 environment also have antiviral activity. R espiratory syncytial virus (RSV) is a serious lower respiratory tract infection in infants, the elderly, and the immunocompromised (1-4), resulting in Ͼ130,000 hospitalizations in the United States each year (5, 6). Children who experience acute RSV infection of the lower respiratory tract have an increased likelihood of developing childhood asthma (7). To date, there is no safe and effective RSV vaccine available. This is in part linked to the negative outcome of a 1960s clinical trial using a formalin-inactivated alum-precipitated RSV (FI-RSV) vaccine (8). Children immunized with the FI-RSV vaccine experienced more severe disease following subsequent natural exposure to RSV, with one study showing 69% of immunized children developing pneumonia compared to only 9% of children in the unimmunized control group (9). In a second study, 80% of FI-RSV-immunized infants were hospitalized and two died, compared with only 5% hospitalization and no death in the control group (10). FI-RSV vaccineenhanced illness was clinically characterized as severe primary RSV infection, with bronchiolitis, hypoxemia, and pneumonia. However, in contrast to the neutrophilic inflammation observed during primary RSV infection, the more severe a...

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confidence: 99%

Dual Proinflammatory and Antiviral Properties of Pulmonary Eosinophils in Respiratory Syncytial Virus Vaccine-Enhanced Disease

Townsend

Herrero

et al. 2015

J Virol

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“…Unfortunately, both attenuated live and subunit candidate vaccines induce only modest increases in Abs (29,30). Consequently, a variety of adjuvants are being evaluated for their ability to enhance the immune response to subunit vaccines (31)(32)(33). In addition, genes for immune-enhancing molecules could be introduced into live virus vaccine candidates using the RSV infectious clone.…”

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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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“…Thus, it was hypothesized that the F protein, through TLR4, would act as a molecular adjuvant to enhance the immune response to HA protein to confer enhanced immunity to influenza virus challenge. As the F protein is a major target in the host immune response upon RSV infection (21,92), and RSV F protein vaccine candidates have shown a level of efficacy based on neutralizing properties (42,93), it was also hypothesized that the F protein would not only serve as a vaccine adjuvant for HA but also as a vaccine antigen to RSV. Mice vaccinated with the RSV F protein only, HAϩF, or HA-F were able to mount antibody titers that neutralized RSV viral titers, and addition of the HA component as a dual vaccine did not hamper immunity to F protein.…”

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confidence: 99%

A Novel Influenza Virus Hemagglutinin-Respiratory Syncytial Virus (RSV) Fusion Protein Subunit Vaccine against Influenza and RSV

Turner

Jones

Tompkins

et al. 2013

J Virol

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Influenza A virus and respiratory syncytial virus (RSV) cause substantial morbidity and mortality afflicting the ends of the age spectrum during the autumn through winter months in the United States. The benefit of vaccination against RSV and influenza using a subunit vaccine to enhance immunity and neutralizing antibody was investigated. Influenza virus hemagglutinin (HA) and RSV fusion (F) protein were tested as vaccine components alone and in combination to explore the adjuvant properties of RSV F protein on HA immunity. Mice vaccinated with HA and F exhibited robust immunity that, when challenged, had reduced viral burden for both influenza and RSV. These studies show an enhancing and cross-protective benefit of F protein for anti-HA immunity.

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Adjuvants influence the quantitative and qualitative immune response in BALBc mice immunized with respiratory syncytial virus FG subunit vaccine

Cited by 67 publications

References 29 publications

Dual Proinflammatory and Antiviral Properties of Pulmonary Eosinophils in Respiratory Syncytial Virus Vaccine-Enhanced Disease

Dual Proinflammatory and Antiviral Properties of Pulmonary Eosinophils in Respiratory Syncytial Virus Vaccine-Enhanced Disease

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

A Novel Influenza Virus Hemagglutinin-Respiratory Syncytial Virus (RSV) Fusion Protein Subunit Vaccine against Influenza and RSV

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