Respiratory Syncytial Virus Disease in Infants Despite Prior Administration of Antigenic Inactivated Vaccine12

Kim, Hyun Wha; Canchola, Jose G.; Brandt, Carl D.; Pyles, Gloria; Chanock, Robert M.; Jensen, Keith E.; Parrott, Robert H.

doi:10.1093/oxfordjournals.aje.a120955

Cited by 1,774 publications

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“…Vaccine-enhanced disease has been seen in the human with two members of the Paramyxoviridae family, measles and hRSV [7,11]. Similar enhancement has been shown experimentally in cotton rats with hRSV [20,22], measles [18], parainfluenza 3 [16], and now hMPV.…”

Section: Discussionsupporting

confidence: 54%

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Human metapneumovirus: Enhanced pulmonary disease in cotton rats immunized with formalin-inactivated virus vaccine and challenged

Yim¹,

Cragin²,

Boukhvalova³

et al. 2007

Vaccine

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Cotton rats (Sigmodon hispidus) are susceptible to the recently discovered human metapneumovirus (hMPV), an agent closely related to human respiratory syncytial virus. Since certain respiratory syncytial virus vaccines can induce enhanced disease upon viral challenge, we have done similar experiments with hMPV in cotton rats. Young adult cotton rats were vaccinated with a formalininactivated preparation of hMPV strain C-85473, or with a mock preparation of the vaccine on day 0 and again on day 28. All animals were challenged intranasally on day 49 with 10 7 TCID 50 of the same hMPV strain. Animals were sacrificed on days 4, 7, and 10 post-challenge and lungs were removed for viral quantitation, histopathology, and cytokine mRNA expression analysis (interferongamma (IFN-γ) and interleukin-4 (IL-4)). Although the vaccinated animals showed almost complete protection from viral replication in the lungs (<10 2.0 TCID 50 per gram), there was a dramatic increase in the lung pathology, particularly the interstitial pneumonitis and alveolitis with elevated serum neutralizing antibody titer prior to challenge. Cytokine profiles were distinctive from those observed during primary infection and re-infection. The data raise safety concerns for hMPV vaccine preparations.

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Section: Discussionsupporting

confidence: 54%

“…The use of an early formalin-inactivated hRSV vaccine (FI-hMPV) together with natural environmental challenge with the virus resulted in severe pulmonary disease, hospitalization and two deaths among the immunized children [11]. We have described the lung tissues from the fatal cases in detail [20].…”

Section: Introductionmentioning

confidence: 99%

Human metapneumovirus: Enhanced pulmonary disease in cotton rats immunized with formalin-inactivated virus vaccine and challenged

Yim¹,

Cragin²,

Boukhvalova³

et al. 2007

Vaccine

View full text Add to dashboard Cite

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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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“…The moderate to high levels of maternally derived serum antibody, present in the sera of infants of this age, does not appear to protect against infection. In spite of attempts to produce an inactivated vaccine Kim et al 1969a) the problem of prevention of infection with this virus remains unsolved. In fact these studies with inactivated vaccine have shown that those who have been given vaccine fare worse than those without, on natural infection with R.S.…”

Section: Introductionmentioning

confidence: 99%

The local antibody response to R.S. virus infection in the respiratory tract

Scott

Gardner

1974

J. Hyg.

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SUMMARYNasopharyngeal secretions were taken during the acute phase of illness from 66 infants and children admitted to hospital with lower respiratory tract infections. Second secretions were taken, after an interval of 7 days, from 33 of these patients. A significant increase in neutralizing activity to R.S. virus was demonstrated in the nasopharyngeal secretions of patients in response to severe R.S. virus infection.Seventeen out of 25 patients (68 %) with R.S. virus infections developed a rise in secretory neutralizing titre, compared with only 1 out of 8 patients (13 %) with respiratory infections not involving R.S. virus.A high titre of secretory neutralizing activity was found more often in the acute phase of illness in patients with R.S. virus infections, especially bronchiolitis, than in patients with respiratory infections not involving R.S. virus. A quantitative analysis of the immunoglobulins present in the secretions indicated that IgA was the only immunoglobulin consistently present at a detectable concentration. The geometric mean values of IgA, IgM and IgG in the secre tions examined were found to be 22-3 ,4 3 and 5-3 mg./100 ml. respectively.The neutralizing activity against R.S. virus, present in the secretions, was shown to be due to specific IgA antibody. This was accomplished by removing the neutralizing activity in two secretions by absorption with anti-IgA serum.

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Respiratory Syncytial Virus Disease in Infants Despite Prior Administration of Antigenic Inactivated Vaccine12

Cited by 1,774 publications

References 0 publications

Human metapneumovirus: Enhanced pulmonary disease in cotton rats immunized with formalin-inactivated virus vaccine and challenged

Human metapneumovirus: Enhanced pulmonary disease in cotton rats immunized with formalin-inactivated virus vaccine and challenged

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

The local antibody response to R.S. virus infection in the respiratory tract

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