Translational sciences approach to RSV vaccine development

Kurzweil, Vanessa; Tang, Roderick S.; Galinski, Mark S.; Wang, Kathy; Zuo, Fengrong; Cherukuri, Anu; Gasser, Robert A.; Malkin, Elissa; Sifakis, Frangiscos; Esser, Mark T.

doi:10.1586/14760584.2013.824706

Cited by 13 publications

(11 citation statements)

References 144 publications

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“…In summary, despite some limitations, our inference methodology provides a consistent relation between the incidence of influenza and RSV and the associated hospitalization outcomes, a relation that is linear (proportional) and avoiding parametric assumptions about the weekly hospitalization rates not associated with the two pathogens. The results in our study contribute to the understanding of the hospitalization burden associated with influenza and respiratory syncytial virus, stressing the need for the mitigation of the impact of the annual epidemics corresponding to those two respiratory viruses, including the possibility of developing a vaccine for RSV …”

Section: Discussionmentioning

confidence: 80%

“…The results in our study contribute to the understanding of the hospitalization burden associated with influenza and respiratory syncytial virus, stressing the need for the mitigation of the impact of the annual epidemics corresponding to those two respiratory viruses, including the possibility of developing a vaccine for RSV. 3,30…”

Section: Discussionmentioning

confidence: 99%

“…The period analyzed was between calendar week 36 of 2003 and calendar week 34, 2011, with calendar week 27, 2008 discarded to ensure a 52-week periodicity each season. An influenza season was defined as calendar week 40 through week 20 of the next year, except for the spring/summer of 2009 (weeks [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]2009); separate estimates were calculated for this period corresponding to the first wave of the A/H1N1 influenza pandemic. We defined the weekly incidence proxies for the major influenza (sub) types (A/H1N1, A/H3N2 and B) and RSV as follows: the weekly incidence proxy for an influenza subtype was the percent of emergency department (ED) visits in NYC classified as influenza-like illness multiplied by the percent of respiratory specimens which were positive for a given subtype; the weekly incidence proxy for RSV was the rate of hospitalizations coded for RSV bronchiolitis for age <1.…”

Section: Methodsmentioning

confidence: 99%

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Estimating the hospitalization burden associated with influenza and respiratory syncytial virus in New York City, 2003–2011

Goldstein

Greene

Olson

et al. 2015

Influenza Resp Viruses

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BackgroundHospitalization burden associated with influenza and respiratory syncytial virus (RSV) is uncertain due to ambiguity in the inference methodologies employed for its estimation.ObjectivesUtilization of a new method to quantitate the above burden.MethodsWeekly hospitalization rates for several principal diagnoses from 2003 to 2011 in New York City by age group were regressed linearly against incidence proxies for the major influenza subtypes and RSV adjusting for temporal trends and seasonal baselines.ResultsAverage annual rates of influenza-associated respiratory hospitalizations per 100 000 were estimated to be 129 [95% CI (79, 179)] for age <1, 36·3 (21·6, 51·4) for ages 1–4, 10·6 (7·5, 13·7) for ages 5–17, 25·6 (21·3, 29·8) for ages 18–49, 65·5 (54·0, 76·9) for ages 50–64, 125 (105, 147) for ages 65–74, and 288 (244, 331) for ages ≥75. Additionally, influenza had a significant contribution to hospitalization rates with a principal diagnosis of septicemia for ages 5–17 [0·76 (0·1, 1·4)], 18–49 [1·02 (0·3, 1·7)], 50–64 [4·0 (1·7, 6·3)], 65–74 [8·8 (2·2, 15·6)], and ≥75 [38·7 (25·7, 52·9)]. RSV had a significant contribution to the rates of respiratory hospitalizations for age <1 [1900 (1740, 2060)], ages 1–4 [117 (70, 167)], and ≥75 [175 (44, 312)] [including chronic lower respiratory disease, 90 (43, 140)] as well as pneumonia & influenza hospitalizations for ages 18–49 [6·2 (1·1, 11·3)] and circulatory hospitalizations for ages ≥75 [199 (13, 375)].ConclusionsThe high burden of RSV hospitalizations among young children and seniors age ≥75 suggests the need for additional control measures such as vaccination to mitigate the impact of annual RSV epidemics. Our estimates for influenza-associated hospitalizations provide further evidence of the burden of morbidity associated with influenza, supporting current guidelines regarding influenza vaccination and antiviral treatment.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Estimating the hospitalization burden associated with influenza and respiratory syncytial virus in New York City, 2003–2011

Goldstein

Greene

Olson

et al. 2015

Influenza Resp Viruses

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“…Studies have found that the RSV-specific memory CD8 ϩ T cells are reduced in the peripheral blood of healthy elderly adults (10,11), and we have previously shown that RSV-specific IFN-␥ T cell responses are diminished in subjects 65 years and older (12). A number of studies have found that higher neutralizing antibody levels in serum correlate with reduced risk for RSV infection at all ages (13,14); thus, we believe that an effective vaccine in the elderly will need to induce high levels of RSV-neutralizing antibodies and elicit a T helper type 1 (Th1)-like cellular immune response denoted by IFN-␥ production.…”

mentioning

confidence: 88%

Enzyme-Linked Immunospot Assay for Detection of Human Respiratory Syncytial Virus F Protein-Specific Gamma Interferon-Producing T Cells

Patton¹,

Aslam²,

Lin³

et al. 2014

Clin. Vaccine Immunol.

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Respiratory syncytial virus (RSV) causes significant disease in elderly adults, and we have previously reported that individuals 65 years of age and older have reduced RSV F protein-specific gamma interferon (IFN-␥)-producing T cells compared to healthy younger adults. To measure RSV F-specific memory T cell responses in the elderly following infection or vaccination, we optimized and qualified an IFN-␥ enzyme-linked immunospot (ELISPOT) assay. Since peripheral blood mononuclear cells (PBMC) from the elderly could be more fragile, we established optimal cryopreservation techniques and minimal viability acceptance criteria. The number of cells per well, types and concentrations of stimulation antigens, and incubation times were evaluated to maximize assay sensitivity and precision. The optimized assay uses 300,000 cells/well, 2 g/ml of an RSV F peptide pool (RSV Fpp), and incubation for 22 ؎ 2 h in serum-free CTL-Test medium. The assay was qualified by 3 analysts using 3 RSV F-responding donor PBMC samples (high, medium, and low responders) tested on 5 different assay days. The assay sensitivity or limit of detection (LOD) was determined to be 21 spot-forming cells (SFC) per 10 6 PBMC, and the lower limit of quantitation (LLOQ) was estimated to be 63 SFC/10 6 PBMC. The intra-and interassay percent coefficients of variation (CV) were <10.5% and <31%, respectively. The results of the qualification study demonstrate that a robust, precise, and sensitive IFN-␥ ELISPOT assay has been developed that is fit for measuring RSV F-specific IFN-␥ T cell responses in subjects enrolled in a vaccine clinical trial or in epidemiology studies.

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“…A live virus vaccine trial has shown that a particular vaccine candidate, MEDI-559, is safe, although effectiveness has not been proven [57]. Other strategies include subunit RSV vaccines, the use of DNAconjugate vaccines to boost antigen presentation, and further development of passive antibody prophylaxis that is focused on F or G proteins [52,[58][59][60][61][62][63][64][65][66][67][68][69][70][71][72]. An additional challenge with all of these strategies is that effective vaccine studies in animals have not been translated into successful human trials.…”

Section: Respiratory Syncytial Virus-how To Develop An Effective Vaccmentioning

confidence: 99%

Unmet Needs in Respiratory Diseases

Chang

2013

Clinic Rev Allerg Immunol

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The care of patients with respiratory diseases has improved vastly in the past 50 years. In spite of that, there are still massive challenges that have not been resolved. Although the incidence of tuberculosis has decreased in the developed world, it is still a significant public health problem in the rest of the world. There are still over 2 million deaths annually from tuberculosis, with most of these occurring in the developing world. Even with the development of new pharmaceuticals to treat tuberculosis, there is no indication that the disease will be eradicated. Respiratory syncytial virus, severe acute respiratory syndrome, and pertussis are other respiratory infectious diseases with special problems of their own, from vaccine development to vaccine coverage. Asthma, one of the most common chronic diseases in children, still accounts for significant mortality and morbidity, as well as high health care costs worldwide. Even in developed countries such as the USA, there are over 4,000 deaths per year. Severe asthma presents a special problem, but the question is whether there can be one treatment pathway for all patients with severe asthma. Severe asthma is a heterogeneous disease with many phenotypes and endotypes. The gene for cystic fibrosis was discovered over 24 years ago. The promise of gene therapy as a cure for the disease has fizzled out, and while new antimicrobials and other pharmaceuticals promise improved longevity and better quality of life, the average life span of a patient with cystic fibrosis is still at about 35 years. What are the prospects for gene therapy in the twenty-first century? Autoimmune diseases of the lung pose a different set of challenges, including the development of biomarkers to diagnose and monitor the disease and biological modulators to treat the disease.

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Translational sciences approach to RSV vaccine development

Cited by 13 publications

References 144 publications

Estimating the hospitalization burden associated with influenza and respiratory syncytial virus in New York City, 2003–2011

Estimating the hospitalization burden associated with influenza and respiratory syncytial virus in New York City, 2003–2011

Enzyme-Linked Immunospot Assay for Detection of Human Respiratory Syncytial Virus F Protein-Specific Gamma Interferon-Producing T Cells

Unmet Needs in Respiratory Diseases

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