Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-5 (of 5 Records) |
Query Trace: Barnum O[original query] |
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Continuing contributions of field epidemiology training programs to global COVID-19 response
Bell E , Mittendorf C , Meyer E , Barnum O , Reddy C , Williams S , Baggett H , Turcios-Ruiz R . Emerg Infect Dis 2022 28 (13) S129-s137 We documented the contributions of Field Epidemiology Training Program (FETP) trainees and graduates to global COVID-19 preparedness and response efforts. During February-July 2021, we conducted surveys designed in accordance with the World Health Organization's COVID-19 Strategic Preparedness and Response Plan. We quantified trainee and graduate engagement in responses and identified themes through qualitative analysis of activity descriptions. Thirty-two programs with 2,300 trainees and 7,372 graduates reported near-universal engagement across response activities, particularly those aligned with the FETP curriculum. Graduates were more frequently engaged than were trainees in pandemic response activities. Common themes in the activity descriptions were epidemiology and surveillance, leading risk communication, monitoring and assessment, managing logistics and operations, training and capacity building, and developing guidelines and protocols. We describe continued FETP contributions to the response. Findings indicate the wide-ranging utility of FETPs to strengthen countries' emergency response capacity, furthering global health security. |
Mutating the CX3C motif in the G protein should make a live respiratory syncytial virus vaccine safer and more effective.
Boyoglu-Barnum S , Todd SO , Meng J , Barnum TR , Chirkova T , Haynes LM , Jadhao SJ , Tripp RA , Oomens AG , Moore ML , Anderson LJ . J Virol 2017 91 (10) Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. Through a CX3C chemokine motif (182CWAIC186) in the G protein, RSV binds to the corresponding chemokine receptor, CX3CR1. Since RSV binding to CX3CR1 contributes to disease pathogenesis, we investigated whether a mutation in the CX3C motif by insertion of an alanine A186 within the CX3C motif to CX4C (182CWAIAC187), known to block binding to CX3CR1, might decrease disease. We studied the effect of the CX4C mutation in two strains of RSV (A2 and r19F) in a mouse challenge model. We included the RSV r19F because it induces mucous production and airway resistance, two manifestations of RSV infection in humans, in mice. Compared to wildtype virus (wt), mice infected with the CX4C had a 0.7 to 1.2 log10-fold lower virus titer in the lung at 5 days p.i. and had markedly reduced weight loss, pulmonary inflammatory cell infiltration, mucous production, and airway resistance after challenge. This decrease in disease was not dependent on decrease in virus replication but did correspond to a decrease in pulmonary Th2 and inflammatory cytokines. Mice infected with CX4C viruses also had higher antibody titers and a Th1 biased T cell memory response at 75 days pi. These results suggest that the CX4C mutation in the G protein could improve the safety and efficacy of a live attenuated RSV vaccine.Importance RSV binds to the corresponding chemokine receptor, CX3CR1, through a CX3C chemokine motif (182CWAIC186) in the G protein. RSV binding to CX3CR1 contributes to disease pathogenesis, therefore, we investigated whether a mutation in the CX3C motif by insertion of an alanine A186 within the CX3C motif to CX4C (182CWAIAC187), known to block binding to CX3CR1, might decrease disease. The effect of this mutation and treatment with the F(ab')2 form of the anti-RSV G 131-2G mAb show that mutating the CX3C motif to CX4C blocks much of the disease and immune modulation associated with the G protein and should improve the safety and efficacy of a live attenuated RSV vaccine. |
An anti-G protein monoclonal antibody treats RSV disease more effectively than an anti-F monoclonal antibody in BALB/c mice
Boyoglu-Barnum S , Todd SO , Chirkova T , Barnum TR , Gaston KA , Haynes LM , Tripp RA , Moore ML , Anderson LJ . Virology 2015 483 117-125 Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. To clarify the potential for an anti-G mAb, 131-2G which has both anti-viral and anti-inflammatory effects, to effectively treat RSV disease, we determined the kinetics of its effect compared to the effect of the anti-F mAb, 143-6C on disease in mice. Treatment administered three days after RSV rA2-line19F (r19F) infection showed 131-2G decreased breathing effort, pulmonary mucin levels, weight loss, and pulmonary inflammation earlier and more effectively than treatment with mAb 143-6C. Both mAbs stopped lung virus replication at day 5 post-infection. These data show that, in mice, anti-G protein mAb is superior to treating disease during RSV infection than an anti-F protein mAb similar to Palivizumab. This combination of anti-viral and anti-inflammatory activity makes 131-2G a promising candidate for treating for active human RSV infection. |
Prophylaxis with a respiratory syncytial virus (RSV) anti-G protein monoclonal antibody shifts the adaptive immune response to RSV rA2-line19F infection from Th2 to Th1 in BALB/c mice
Boyoglu-Barnum S , Chirkova T , Todd SO , Barnum TR , Gaston KA , Jorquera P , Haynes LM , Tripp RA , Moore ML , Anderson LJ . J Virol 2014 88 (18) 10569-83 Respiratory syncytial virus (RSV) is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. In the present study, we investigated the effect of prophylactic treatment with the intact and F(ab')2 forms of an anti-G protein monoclonal antibody (mAb), 131-2G, on the humoral and cellular adaptive immune response to RSV rA2-line19F (r19F) challenge in BALB/c mice. The F(ab')2 form of 131-2G does not decrease virus replication but intact 131-2G does. The serum specimens for antibodies and spleen cells for memory T cell responses to RSV antigens were analyzed at 30, 45, 75 and 95 p.i. with/without prior treatment with 131-2G. The ratios of Th2/Th1 antibody isotypes at each time p.i indicated that both forms of mAb 131-2G shifted the subclass response from a Th2 (IgG1 and IgG2b) to a Th1 (IgG2A) bias. The ratio of IgG1/IgG2A antibody titer was 3-fold to 10-fold higher for untreated than mAb treated mice. There was also some increase in IgG (22%+/-13 increase) and neutralization (32% increase) in antibodies with mAb 131-2G prophylaxis at 75 days p.i. Treatment with 131-2G significantly (p≤0.001) decreased the percent of IL-4 positive CD4 and CD8 in RSV stimulated spleen cells at all times p.i. while percent of IFN-gamma T cells significantly (p≤0.001) increased ≥75 days p.i. The shift from a Th2 to a Th1 biased T cell response in treated compared to untreated mice likely was directed by the much higher levels of T-box transcription factor (Tbet) (≥45% vs <10%) in CD4 and CD8 T cells and lower levels of Gata-3 (≤2% vs ≥6%) in CD4 T cells in peptide stimulated, day 75 p.i. spleen cells. These data show that the RSV G protein affects both humoral and cellular adaptive immune responses and induction of 131-2G-like antibodies might improve the safety and long term efficacy of an RSV vaccine. IMPORTANCE: The data in this report suggest that the RSV G protein not only contributes to disease but also dampens the host immune response to infection. Both effects of G likely contribute to difficulties in achieving an effective vaccine. The ability of mAb 131-2G to block these effects of G suggests that inducing antibodies similar to 131-2G should prevent disease and enhance the adaptive immune response with later RSV infection. The fact that 131-2G binds to the 13 aa region conserved among all strains and flanking sequences are conserved within Group A or within Group B strains, simplifies the task of developing a vaccine to induce 131-2G-like antibodies. If our findings in mice apply to humans, then including the 131-2G binding region of G in a vaccine should improve its safety and efficacy. |
A respiratory syncytial virus (RSV) anti-G protein F(ab')2 monoclonal antibody suppresses mucous production and breathing effort in RSV rA2-line19F-infected BALB/c mice
Boyoglu-Barnum S , Gaston KA , Todd SO , Boyoglu C , Chirkova T , Barnum TR , Jorquera P , Haynes LM , Tripp RA , Moore ML , Anderson LJ . J Virol 2013 87 (20) 10955-67 Respiratory syncytial virus (RSV) belongs to the family Paramyxoviridae and is the single most important cause of serious lower respiratory tract infections in young children, yet no highly effective treatment or vaccine is available. Increased airway resistance and increased airway mucin production are two manifestations of RSV infection in children. RSV rA2-line19F infection induces pulmonary mucous production and increased breathing effort in BALB/c mice and provides a way to assess these manifestations of RSV disease in an animal model. In the present study, we investigated the effect of prophylactic treatment with the F(ab')2 form of the anti-G protein monoclonal antibody (MAb) 131-2G on disease in RSV rA2-line19F-challenged mice. F(ab')2 131-2G does not affect virus replication. It and the intact form that does decrease virus replication prevented increased breathing effort and airway mucin production, as well as weight loss, pulmonary inflammatory-cell infiltration, and the pulmonary substance P and pulmonary Th2 cytokine levels that occur in mice challenged with this virus. These data suggest that the RSV G protein contributes to prominent manifestations of RSV disease and that MAb 131-2G can prevent these manifestations of RSV disease without inhibiting virus infection. |
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