An Epidemiologic Study of Altered Clinical Reactivity to Respiratory Syncytial (Rs) Virus Infection in Children Previously Vaccinated With an Inactivated Rs Virus Vaccine

Kapikian, Albert Z.; Mitchell, Richard; Chanock, Robert M.; Shvedoff, Ruth A.; Stewart, Claire Emma

doi:10.1093/oxfordjournals.aje.a120954

Cited by 942 publications

(568 citation statements)

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“…Indeed, pathology observed following primary infection in infants is largely immune mediated [10,11]. Furthermore, there is a risk of serious immunopathology upon RSV infection secondary to a failed vaccination, as demonstrated by clinical trials conducted in the 1960s using formalininactivated RSV (FI-RSV) [12,13]. Although the etiology of this enhanced disease has never been fully elucidated, studies in animal models have suggested that FI-RSV leads to a Th2-skewed CD4 + T cell response that not only fails to clear the virus but also triggers the recruitment of eosinophils [14,15].…”

Section: Immunity To Infectionmentioning

confidence: 99%

Intranasal immunisation with inactivated RSV and bacterial adjuvants induces mucosal protection and abrogates eosinophilia upon challenge

et al. 2006

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We have previously shown that following intranasal exposure to influenza virus, specific plasma cells are generated in the nasal-associated lymphoid tissue (NALT) and maintained for the life of the animal. However, we also showed that following infection with respiratory syncytial virus (RSV), specific plasma cells are generated in the NALT but wane quickly and are not maintained even after challenge, even though RSVspecific serum antibody responses remain robust. Only infection with influenza virus generated sterilising immunity, implying a role for these long-lived plasma cells in protection. We show here that the RSV-specific IgA NALT plasma cell population and lung antibody levels can be substantially boosted, both at acute and memory time points, by intranasal immunisation with inactivated RSV (iRSV) in combination with bacterial outer membrane vesicles (OMV) compared to live RSV alone. Finally, challenge with live RSV showed that immunisation with iRSV and OMV protect against both virus replication in the lung and the eosinophil infiltrate generated by either live RSV or iRSV alone. These data show that immunisation with iRSV and OMV maintains a NALT RSV-specific plasma cell population and generates an efficient protective immune response following RSV infection.See accompanying commentary: http://dx

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Section: Immunity To Infectionmentioning

confidence: 99%

Intranasal immunisation with inactivated RSV and bacterial adjuvants induces mucosal protection and abrogates eosinophilia upon challenge

et al. 2006

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“…In the United States, it is estimated that Ͼ100,000 RSV-infected young children and elderly are hospitalized annually for supportive care (1,2). The first candidate vaccine, formalin-inactivated RSV, was associated with enhanced disease when vaccinated children were subsequently naturally infected with RSV (5). No RSV subunit or live virus vaccine tested to date in humans has been shown to be effective.…”

mentioning

confidence: 99%

Potent High-Affinity Antibodies for Treatment and Prophylaxis of Respiratory Syncytial Virus Derived from B Cells of Infected Patients

Collarini

Lee

Foord

et al. 2009

The Journal of Immunology

111

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Native human Abs represent attractive drug candidates; however, the low frequency of B cells expressing high-quality Abs has posed a barrier to discovery. Using a novel single-cell phenotyping technology, we have overcome this barrier to discover human Abs targeting the conserved but poorly immunogenic central motif of respiratory syncytial virus (RSV) G protein. For the entire cohort of 24 subjects with recent RSV infection, B cells producing Abs meeting these stringent specificity criteria were rare, <10 per million. Several of the newly cloned Abs bind to the RSV G protein central conserved motif with very high affinity (Kd 1–24 pM). Two of the Abs were characterized in detail and compared with palivizumab, a humanized mAb against the RSV F protein. Relative to palivizumab, the anti-G Abs showed improved viral neutralization potency in vitro and enhanced reduction of infectious virus in a prophylaxis mouse model. Furthermore, in a mouse model for postinfection treatment, both anti-G Abs were significantly more effective than palivizumab at reducing viral load. The combination of activity in mouse models for both prophylaxis and treatment makes these high-affinity human-derived Abs promising candidates for human clinical testing.

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“…1 There is no licensed RSV vaccine since the tragic failure of formalin inactivated RSV (FI-RSV) in 1960s). 2,3 Numerous vaccine platforms have been tested, which include subunit soluble RSV F (fusion) and G (attachment) glycoproteins, vectored vaccines, and live attenuated vaccines (reviewed in 4). Non-replicating subunit vaccines have the safety concerns of vaccineenhanced disease after vaccination and infection.…”

Section: Introductionmentioning

confidence: 99%

Virus-like particle vaccines containing F or F and G proteins confer protection against respiratory syncytial virus without pulmonary inflammation in cotton rats

Hwang

Kim

Lee

et al. 2017

Human Vaccines & Immunotherapeutics

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Vaccine-enhanced disease has been a major obstacle in developing a safe vaccine against respiratory syncytial virus (RSV). This study demonstrates the immunogenicity, efficacy, and safety of virus-like particle (VLP) vaccines containing RSV F (F VLP), G (G VLP), or F and G proteins (FG VLP) in cotton rats. RSV specific antibodies were effectively induced by vaccination of cotton rats with F VLP or FG VLP vaccines. After challenge, lung RSV clearance was observed with RSV F, G, FG VLP, and formalin inactivated RSV (FI-RSV) vaccines. Upon RSV infection, cotton rats with RSV VLP vaccines were protected against airway hyperresponsiveness and weight loss, which are different from FI-RSV vaccination exhibiting vaccine-enhanced disease of airway obstruction, weight loss, and severe histopathology with eosinophilia and mucus production. FG VLP and F VLP vaccines did not cause pulmonary inflammation whereas G VLP induced moderate lung inflammation with eosinophilia and mucus production. In particular, F VLP and FG VLP vaccines were found to be effective in inducing antibody secreting cell responses in bone marrow and lymphoid organs as well as avoiding the induction of T helper type 2 cytokines. These results provide further evidence to develop a safe RSV vaccine based on VLP platforms.

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An Epidemiologic Study of Altered Clinical Reactivity to Respiratory Syncytial (Rs) Virus Infection in Children Previously Vaccinated With an Inactivated Rs Virus Vaccine

Cited by 942 publications

References 0 publications

Intranasal immunisation with inactivated RSV and bacterial adjuvants induces mucosal protection and abrogates eosinophilia upon challenge

Intranasal immunisation with inactivated RSV and bacterial adjuvants induces mucosal protection and abrogates eosinophilia upon challenge

Potent High-Affinity Antibodies for Treatment and Prophylaxis of Respiratory Syncytial Virus Derived from B Cells of Infected Patients

Virus-like particle vaccines containing F or F and G proteins confer protection against respiratory syncytial virus without pulmonary inflammation in cotton rats

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