Antibody neutralization of retargeted measles viruses

Lech, Patrycja; Pappoe, Roland; Nakamura, Takafumi; Tobin, Gregory J.; Nara, Peter L.; Russell, Stephen J.

doi:10.1016/j.virol.2014.01.027

Cited by 19 publications

(13 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…infusion since this would allow the infection of tumor (metastases) at multiple sites. In such applications, the presence of preexisting circulating neutralizing antibodies (NABs) directed against the therapeutic virus is considered a major obstacle for an effective delivery [ 77 , 78 , 79 ]. In the human population most individuals are in their childhood exposed to reoviruses and hence carry NABs [ 80 , 81 ].…”

Section: Reovirus and Its Relation With Neutralizing Antibodiesmentioning

confidence: 99%

Exploring Reovirus Plasticity for Improving Its Use as Oncolytic Virus

Kemp

Hoeben

Wollenberg

2015

Viruses

View full text Add to dashboard Cite

Reoviruses are non-enveloped viruses with a segmented double stranded RNA genome. In humans, they are not associated with serious disease. Human reoviruses exhibit an inherent preference to replicate in tumor cells, which makes them ideally suited for use in oncolytic virotherapies. Their use as anti-cancer agent has been evaluated in several clinical trials, which revealed that intra-tumoral and systemic delivery of reoviruses are well tolerated. Despite evidence of anti-tumor effects, the efficacy of reovirus in anti-cancer monotherapy needs to be further enhanced. The opportunity to treat both the primary tumor as well as metastases makes systemic delivery a preferred administration route. Several pre-clinical studies have been conducted to address the various hurdles connected to systemic delivery of reoviruses. The majority of those studies have been done in tumor-bearing immune-deficient murine models. This thwarts studies on the impact of the contribution of the immune system to the tumor cell eradication. This review focuses on key aspects of the reovirus/host-cell interactions and the methods that are available to modify the virus to alter these interactions. These aspects are discussed with a focus on improving the reovirus’ antitumor efficacy.

show abstract

Section: Reovirus and Its Relation With Neutralizing Antibodiesmentioning

confidence: 99%

Exploring Reovirus Plasticity for Improving Its Use as Oncolytic Virus

Kemp

Hoeben

Wollenberg

2015

Viruses

View full text Add to dashboard Cite

show abstract

“…The following anti-MeV-H protein MAbs used for neutralization were previously described: BH129, BH047, BH059 (69), BH101, BH026 (70), BH141 (71), and BH097 (72). Protein G affinity-purified MAbs were used, except for BH141 and BH059.…”

Section: Methodsmentioning

confidence: 99%

Antigenic Drift Defines a New D4 Subgenotype of Measles Virus

Muñoz-Alía

Russell

2017

J Virol

Self Cite

View full text Add to dashboard Cite

The measles virus hemagglutinin (MeV-H) protein is the main target of protective neutralizing antibodies. Using a panel of monoclonal antibodies (MAbs) that recognize known major antigenic sites in MeV-H, we identified a D4 genotype variant that escapes neutralization by MAbs targeting the neutralizing epitope (NE) antigenic site. By site-directed mutagenesis, L249P was identified as the critical mutation disrupting the NE in this genotype D4 variant. Forty-two available D4 genotype gene sequences were subsequently analyzed and divided into 2 groups according to the presence or absence of the L249P MeV-H mutation. Further analysis of the MeV-N gene sequences of these 2 groups confirmed that they represent clearly definable, sequence-divergent D4 subgenotypes, which we named subgenotypes D4.1 and D4.2. The subgenotype D4.1 MeVs were isolated predominantly in Kenya and Ethiopia, whereas the MAb-resistant subgenotype D4.2 MeVs were isolated predominantly in France and Great Britain, countries with higher vaccine coverage rates. Interestingly, D4.2 subgenotype viruses showed a trend toward diminished susceptibility to neutralization by human sera pooled from approximately 60 to 80 North American donors. Escape from MAb neutralization may be a powerful epidemiological surveillance tool to monitor the evolution of new MeV subgenotypes.IMPORTANCE Measles virus is a paradigmatic RNA virus, as the antigenic composition of the vaccination has not needed to be updated since its discovery. The vaccine confers protection by inducing neutralizing antibodies that interfere with the function of the hemagglutinin protein. Viral strains are indistinguishable serologically, although characteristic nucleotide sequences differentiate 24 genotypes. In this work, we describe a distant evolutionary branch within genotype D4. Designated subgenotype D4.2, this virus is distinguishable by neutralization with vaccine-induced monoclonal antibodies that target the neutralizing epitope (NE). The subgenotype D4.2 viruses have a higher predominance in countries with intermediary levels of vaccine coverage. Our studies demonstrate that subgenotype D4.2 lacks epitopes associated with half of the known antigenic sites, which significantly impacts our understanding of measles virus evolution.KEYWORDS virus evolution, antibody-mediated neutralization, antigenic variation, measles virus hemagglutinin, viral epitopes, measles virus genotypes, immune evasion M easles ranks as one of the most deadly diseases in the history of humankind (1, 2). The advent of an effective measles virus (MeV) vaccine 46 years ago dramatically reduced the number of measles deaths (3), making the MeV live-attenuated vaccine one of the most successful public health interventions ever undertaken (4, 5). Nonetheless, measles is still a leading cause of death globally for children younger than 5 years of age and was responsible for 134,200 deaths in 2015 (6). All 194 WHO member states have committed to reducing measles deaths, and the Global Measles and Rubella

show abstract

“…To overcome this resistance, several groups have demonstrated that PI3K inhibitors (36), proteasome inhibitors (36), or rapamycin (37) sensitize OV-resistant tumors to virother- mutating key surface residues to reduce viral immunity (51). However, all these strategies have the potential to alter viral tropism (52). Other strategies that reduce viral neutralization are to polymer-coat the virus (53,54) or use liposome-encapsulated OVs (55), thereby blocking antibody recognition and extending the circulation times of the viruses in mice (53)(54)(55).…”

Section: Enhancing the Efficacy Of Ovtsmentioning

confidence: 99%