The effect of rituximab on vaccine responses in patients with immune thrombocytopenia

Nazi, Ishac; Kelton, John G.; Larché, Mark; Snider, Denis P.; Heddle, Nancy M.; Crowther, Mark; Cook, Richard J.; Tinmouth, Alan; Mangel, Joy; Arnold, Donald M.

doi:10.1182/blood-2013-04-494096

Cited by 172 publications

(149 citation statements)

References 49 publications

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“…Quantitative RT-PCR (qRT-PCR) was performed using an Applied Biosystems 7500 real-time PCR system. EID 50 were calculated on the basis of a standard curve generated using a stock of known EID 50 . The total EID 50 for the sample was calculated on the basis of the amount present in the sample volume used for the RT-PCR (140 l) and by adjustment to the total volume used for the wash.…”

mentioning

confidence: 99%

Inclusion of Flagellin during Vaccination against Influenza Enhances Recall Responses in Nonhuman Primate Neonates

Kim

Holbrook

Hayward

et al. 2015

J Virol

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Influenza virus can cause life-threatening infections in neonates and young infants. Although vaccination is a major countermeasure against influenza, current vaccines are not approved for use in infants less than 6 months of age, in part due to the weak immune response following vaccination. Thus, there is a strong need to develop new vaccines with improved efficacy for this vulnerable population. To address this issue, we established a neonatal African green monkey (AGM) nonhuman primate model that could be used to identify effective influenza vaccine approaches for use in young infants. We assessed the ability of flagellin, a Toll-like receptor 5 (TLR5) agonist, to serve as an effective adjuvant in this at-risk population. Four-to 6-day-old AGMs were primed and boosted with inactivated PR8 influenza virus (IPR8) adjuvanted with either wild-type flagellin or inactive flagellin with a mutation at position 229 (m229), the latter of which is incapable of signaling through TLR5. Increased IgG responses were observed following a boost, as well as at early times after challenge, in infants vaccinated with flagellin-adjuvanted IPR8. Inclusion of flagellin during vaccination also resulted in a significantly increased number of influenza virus-specific T cells following challenge compared to the number in infants vaccinated with the m229 adjuvant. Finally, following challenge infants vaccinated with IPR8 plus flagellin exhibited a reduced pathology in the lungs compared to that in infants that received IPR8 plus m229. This study provides the first evidence of flagellin-mediated enhancement of vaccine responses in nonhuman primate neonates. Influenza virus remains one of the leading causes of morbidity and mortality worldwide. Infants less than 6 months of age are particularly vulnerable to development of severe disease following infection (1). Diseases associated with influenza virus infection in children include otitis media, pneumonia, myositis, and croup. While oseltamivir (Tamiflu), one of the two FDA-approved antiinfluenza drugs, can be used in infants aged 2 weeks and older, concerns exist due to the potential for adverse effects, drug resistance, and limited effectiveness in young infants (2).Currently, there are three approved approaches for vaccination against influenza in the United States: intramuscular (i.m.) administration of inactivated influenza virus, intramuscular administration of recombinant hemagglutinin (HA) proteins, and intranasal administration of a live attenuated influenza virus (LAIV). The first is approved for use in individuals aged 6 months and older, the second for use in individuals aged 18 to 49 years, and the last for use in healthy individuals aged 2 to 49 years. Thus, none are approved for use in the vulnerable neonate population. While the lack of approval for the use of these vaccines in the very young may reflect some safety concerns, a principal factor is the poor immune responses elicited in human neonates (3,4).Previous studies, while limited, have shown that an initia...

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confidence: 99%

Inclusion of Flagellin during Vaccination against Influenza Enhances Recall Responses in Nonhuman Primate Neonates

Kim

Holbrook

Hayward

et al. 2015

J Virol

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“…Before acceptance of this approach, additional consideration should be given to (1) impaired response to vaccines after rituximab therapy 22 and potential impact of compromised vaccination with subsequent splenectomy if needed, (2) the relative high cost of therapy and (3) the side effect profile of the additional rituximab and number of patients that would be exposed without potential benefit. 23 …”

Section: Intensification Of Therapy Rituximabmentioning

confidence: 99%

Management of newly diagnosed immune thrombocytopenia: can we change outcomes?

Neunert

2017

Blood Advances

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Immune thrombocytopenia resulting from antibody-mediated platelet destruction combined with impaired platelet production is a common cause of thrombocytopenia. The decision to treat newly diagnosed patients is based on several factors including ceasing hemorrhagic manifestations, increasing the platelet count, prevention of bleeding, and inducing remission.Current standard first-line therapy is a course of corticosteroids. Although this treatment paradigm increases the platelet count in the majority of patients, a high percentage relapse after discontinuation of corticosteroid therapy. For this reason, intensification of first-line therapy that results in superior long-term remission rates would be desirable. This manuscript focuses primarily on adults with idiopathic thrombocytopenic purpura (ITP), highlighting pediatric data and practice when applicable. The primary aim is to outline upfront strategies for treatment-naive patients with ITP to enhance remission rates, taking into account assessment of the risks and benefits of these approaches.

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“…It is also associated with a small but important risk of life-threatening infection-a risk that may be higher in patients previously treated with rituximab, which may cause impaired responses to vaccines. 36 Rituximab, although generally well tolerated, can be associated with infusion reactions and hepatitis B reactivation. 37,38 Thrombopoietin (TPO) receptor agonists, because they are new agents, have an incompletely defined safety profile.…”

Section: Discussionmentioning

confidence: 99%

Five hematologic tests and treatments to question

et al. 2014

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The effect of rituximab on vaccine responses in patients with immune thrombocytopenia

Abstract: Key Points After treatment with rituximab, immunological responses to both polysaccharide and conjugated vaccines are impaired in patients with ITP. Splenectomized patients who received rituximab may be at increased risk of infection because of compromised immune responses to vaccines.

Cited by 172 publications

References 49 publications

Inclusion of Flagellin during Vaccination against Influenza Enhances Recall Responses in Nonhuman Primate Neonates

Inclusion of Flagellin during Vaccination against Influenza Enhances Recall Responses in Nonhuman Primate Neonates

Management of newly diagnosed immune thrombocytopenia: can we change outcomes?

Five hematologic tests and treatments to question

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