The Role of Neutralizing Antibodies in Protection of American Indian Infants Against Respiratory Syncytial Virus Disease

Eick, Angelia A.; Karron, Ruth A.; Shaw, Jana; Thumar, Bhagvanji; Reid, Raymond; Santosham, Mathuram; O'Brien, Katherine L.

doi:10.1097/inf.0b013e31815ac585

Cited by 63 publications

(56 citation statements)

References 18 publications

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“…[21][22][23] Another study highlighted the poor role of antibody concentration in conditioning the severity of RSV disease because it showed that children with high levels of maternally derived neutralizing antibodies, despite having a reduced risk of infection, have disease with the same severity of children with a low antibody concentration when RSV infection occurs. 4 In this study, it was expected that the lack of an association between viral factors and immune response and the severity of the disease does not influence immune response. However, the small number of children with LRTI involved in the study, the moment of viral load determination and the methods used to identify the virus could be the reason for this result.…”

Section: Discussionmentioning

confidence: 92%

“…3 Previous studies have shown that the neutralizing antibody concentration plays a fundamental role in conditioning susceptibility to RSV disease and its severity. 4 High titres of maternally derived neutralizing antibodies to RSV correlate well with the protection of younger infants, 4 and the administration of polyclonal or humanized monoclonal antibodies against RSV has been associated with a significant reduction in the number of severe cases and hospitalizations from RSV infection in high-risk infants. 5 Active immunization with RSV vaccines could reduce most of the clinical, economic and societal problems strictly related to RSV infection.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Antibody response to respiratory syncytial virus infection in children <18 months old

Esposito

Scarselli²,

Lelii

et al. 2016

Human Vaccines & Immunotherapeutics

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The development of a safe and effective respiratory syncytial virus (RSV) vaccine might be facilitated by knowledge of the natural immune response to this virus. The aims of this study were to evaluate the neutralizing antibody response of a cohort of healthy children <18 months old to RSV infection. During the RSV season, 89 healthy children <18 months old were enrolled and followed up weekly for 12 weeks. At each visit, a nasopharyngeal swab was obtained for RSV detection by real-time polymerase chain reaction (PCR). During the study period, 2 blood samples were drawn and they were used to determine RSV geometric mean neutralizing antibody titres (GMT) against RSV. A total of 35 (39.3%) children had RSV detected during the study period. Among RSV-positive patients, children 7 months showed a significantly higher increase in antibody response (p<0.001). A significantly higher number of patients with a 4 -fold increase in GMT were 7 months old (p D 0.02) and presented lower respiratory tract infections (LRTIs) during the study period (p D 0.01). Viral shedding was longer among children aged 7 months (p D 0.06), those with viral load 10 6 copies/mL (p D 0.03), and those with LRTIs during the study period (p D 0.03), but it was not associated with the immune response (p D 0.41). In conclusion, natural RSV infection seems to evoke a low immune response in younger children. To be effective in this infant population, which is at highest risk of developing severe LRTIs, vaccines must be able to induce in the first months of life a stronger immune response than that produced by the natural infection.

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Antibody response to respiratory syncytial virus infection in children <18 months old

Esposito

Scarselli²,

Lelii

et al. 2016

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

show abstract

“…In healthy populations, RSVspecific IgG transfer from pregnant women to infants is an active process resulting in higher antibody titers in the infant than in the mother (8). Several studies have demonstrated a reduced incidence of RSV disease during the first several months after birth that correlates with higher concentrations of RSV-specific maternal antibody (9)(10)(11)(12). Further, prevention of RSV in the mother resulting in reduced transmission to the infant is another potential benefit of vaccinating pregnant women.…”

mentioning

confidence: 99%

Progress toward a Respiratory Syncytial Virus Vaccine

Neuzil

2016

Clin Vaccine Immunol

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Respiratory syncytial virus is the leading cause of serious lower respiratory disease in young children throughout the world. An estimated 3.4 million children younger than 5 years of age are hospitalized each year with severe respiratory syncytial virus (RSV) lower respiratory tract infection, with the highest incidence in children younger than 6 months of age. Up to 200,000 deaths occur annually, with most deaths occurring in children younger than 1 year of age and in developing-country settings (1). Unfortunately, options for prevention and control are limited. No RSV vaccine is licensed anywhere in the world. While prophylactic treatment with RSV-specific neutralizing antibody is effective in reducing RSV morbidity in infants, its use is currently limited to select populations in high-resource settings because of its expense and because of challenges with its delivery (2). Prevention of severe RSV disease through active immunization of infants would be optimal but has been extremely challenging to implement, given the young age by which immunity is necessary and the legacy of vaccine-enhanced illness leading to deaths in a number of young children after receipt of a formalin-inactivated RSV vaccine in the 1960s.In this issue of Clinical and Vaccine Immunology, two articles address important obstacles in the path to a successful RSV vaccine (3, 4). Acosta and colleagues provide a history and perspective on the vaccine-enhanced RSV illness that occurred in the 1960s. The devastating results from those trials have thwarted vaccine efforts for the past 5 decades. The authors summarize the large and important body of work that has informed our understanding of immune responses in seronegative infants. The authors caution that RSV vaccines triggering high levels of interleukin-4 (IL-4) and/or IL-13 are associated with enhanced disease in animal models and should be excluded as potential candidates for infant immunization. Likewise, vaccines eliciting nonneutralizing antibody may also be quite risky in seronegative individuals (3).The second article addresses the important issue of identifying a correlate of protection, which if established could make vaccine licensure easier to achieve. Vissers et al. studied a cohort of infants hospitalized with RSV infection in the Netherlands to determine the importance of serum versus mucosal antibody, presumed to be maternally derived given the young age of the infants (mean, 53 days). The authors found that RSV-specific mucosal IgG concentrations, but not plasma IgG concentrations, inversely correlated with viral load (4). While the results are provocative, the study was limited by its small sample size and cross-sectional design. It will be important to replicate these results in larger populations in other locales. Nonetheless, such innovative work is needed to inform measures of vaccine-induced immunity and accelerate RSV vaccine development.The RSV experience reminds us that vaccine development is by nature a prolonged, risky, and increasingly expensive process. Laborato...

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“…Maternally-derived high affinity RSV-specific serum IgG antibody is the best known correlate of protection against infection in infants (Fig 2d) and it is assumed that the relative rarity of severe RSV disease in the first weeks of life is due to virus-specific maternally derived antibody 44,45,[63][64][65][66][67] . However, some of this protection may be indirect, due to reduced rates of maternal infection in those with high levels of antibody.…”

Section: Rsvmentioning

confidence: 99%

“…Nevertheless, severe RSV infection is consistently associated with low levels of pre-existing serum or cord blood RSV antibody 44,45,[63][64][65][66][67] . Infants in the top .…”

Section: Rsvmentioning

confidence: 99%

Group B streptococcus and respiratory syncytial virus immunisation during pregnancy: a landscape analysis

Heath

Culley

Jones

et al. 2017

The Lancet Infectious Diseases

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The Role of Neutralizing Antibodies in Protection of American Indian Infants Against Respiratory Syncytial Virus Disease

Cited by 63 publications

References 18 publications

Antibody response to respiratory syncytial virus infection in children <18 months old

Antibody response to respiratory syncytial virus infection in children <18 months old

Progress toward a Respiratory Syncytial Virus Vaccine

Group B streptococcus and respiratory syncytial virus immunisation during pregnancy: a landscape analysis

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