Infection of mice with respiratory syncytial virus during neonatal life primes for enhanced antibody and T cell responses on secondary challenge

Tasker, Lynn; Lindsay, Ross; Clarke, B.; Cochrane, Daniel; Hou, Sam

doi:10.1111/j.1365-2249.2008.03591.x

Cited by 32 publications

(29 citation statements)

References 46 publications

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“…6, MAV-1/mock and MAV-1/MAV-1 groups), suggesting the possibility that this lymphocyte population contributes to protective responses induced by primary infection of neonates. A similar protective CD8 T cell response has been described following neonatal RSV infection (37). Additional components of adaptive immunity are likely to contribute to this protective effect.…”

Section: Discussionmentioning

confidence: 61%

Susceptibility to Acute Mouse Adenovirus Type 1 Respiratory Infection and Establishment of Protective Immunity in Neonatal Mice

Procario

Levine

McCarthy

et al. 2012

J Virol

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There is an incomplete understanding of the differences between neonatal immune responses that contribute to the increased susceptibility of neonates to some viral infections. We tested the hypothesis that neonates are more susceptible than adults to mouse adenovirus type 1 (MAV-1) respiratory infection and are impaired in the ability to generate a protective immune response against a second infection. Following intranasal infection, lung viral loads were greater in neonates than in adults during the acute phase but the virus was cleared from the lungs of neonates as efficiently as it was from adult lungs. Lung gamma interferon (IFN-␥) responses were blunted and delayed in neonates, and lung viral loads were higher in adult IFN-␥ ؊/؊ mice than in IFN-␥ ؉/؉ controls. However, administration of recombinant IFN-␥ to neonates had no effect on lung viral loads. Recruitment of inflammatory cells to the airways was impaired in neonates. CD4 and CD8 T cell responses were similar in the lungs of neonates and adults, although a transient increase in regulatory T cells occurred only in the lungs of infected neonates. Infection of neonates led to protection against reinfection later in life that was associated with increased effector memory CD8 T cells in the lungs. We conclude that neonates are more susceptible than adults to acute MAV-1 respiratory infection but are capable of generating protective immune responses.

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Section: Discussionmentioning

confidence: 61%

Susceptibility to Acute Mouse Adenovirus Type 1 Respiratory Infection and Establishment of Protective Immunity in Neonatal Mice

Procario

Levine

McCarthy

et al. 2012

J Virol

View full text Add to dashboard Cite

show abstract

“…Several recent reports have highlighted many important differences in the neonatal T cell response (17, 55–61). However, it is often unclear whether altered behavior of neonatal T cells is due to a less diverse TCR repertoire, lower amounts of TCR avidity, smaller precursor numbers or environmental factors.…”

Section: Discussionmentioning

confidence: 99%

Rapid Proliferation and Differentiation Impairs the Development of Memory CD8+ T Cells in Early Life

Smith

Wissink

Wang

et al. 2014

The Journal of Immunology

103

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Neonates often generate incomplete immunity against intracellular pathogens, although the mechanism of this defect is poorly understood. An important question is whether the impaired development of memory CD8+ T cells in neonates is due to an immature priming environment or lymphocyte-intrinsic defects. Here we show that neonatal and adult CD8+ T cells adopted different fates when responding to equal amounts of stimulation in the same host. While adult CD8+ T cells differentiated into a heterogeneous pool of effector and memory cells, neonatal CD8+ T cells preferentially gave rise to short-lived effector cells and exhibited a distinct gene expression profile. Surprisingly, impaired neonatal memory formation was not due to a lack of responsiveness, but instead because neonatal CD8+ T cells expanded more rapidly than adult cells and quickly became terminally differentiated. Collectively, these findings demonstrate that neonatal CD8+ T cells exhibit an imbalance in effector and memory CD8+ T cell differentiation, which impairs the formation of memory CD8+ T cells in early life.

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“…One possibility is that exposure to RSV antigen in the context of immunologic immaturity and maternal antibody-mediated immunosuppression may have long-term deleterious effects on protective responses. There indeed is evidence from the mouse model that exposure to RSV very early in life results in skewed responses during primary and secondary infection (Culley et al, 2002; Tasker et al, 2008). In addition, viral mechanisms might substantially inhibit the induction of protective immunity.…”

Section: Protective Immunitymentioning

confidence: 99%

Progress in understanding and controlling respiratory syncytial virus: Still crazy after all these years

2011

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Human respiratory syncytial virus (RSV) is a ubiquitous pathogen that infects everyone worldwide early in life and is a leading cause of severe lower respiratory tract disease in the pediatric population as well as in the elderly and in profoundly immunosuppressed individuals. RSV is an enveloped, nonsegmented negative-sense RNA virus that is classified in Family Paramyxoviridae and is one of its more complex members. Although the replicative cycle of RSV follows the general pattern of the Paramyxoviridae, it encodes additional proteins. Two of these (NS1 and NS2) inhibit the host type I and type III interferon (IFN) responses, among other functions, and another gene encodes two novel RNA synthesis factors (M2-1 and M2-2). The attachment (G) glycoprotein also exhibits unusual features, such as high sequence variability, extensive glycosylation, cytokine mimicry, and a shed form that helps the virus evade neutralizing antibodies. RSV is notable for being able to efficiently infect early in life, with the peak of hospitalization at 2–3 months of age. It also is notable for the ability to reinfect symptomatically throughout life without need for significant antigenic change, although immunity from prior infection reduces disease. It is widely thought that re-infection is due to an ability of RSV to inhibit or subvert the host immune response. Mechanisms of viral pathogenesis remain controversial. RSV is notable for a historic, tragic pediatric vaccine failure involving a formalin-inactivated virus preparation that was evaluated in the 1960’s and that was poorly protective and paradoxically primed for enhanced RSV disease. RSV also is notable for the development of a successful strategy for passive immunoprophylaxis of high-risk infants using RSV-neutralizing antibodies. Vaccines and new antiviral drugs are in pre-clinical and clinical development, but controlling RSV remains a formidable challenge.

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Infection of mice with respiratory syncytial virus during neonatal life primes for enhanced antibody and T cell responses on secondary challenge

Cited by 32 publications

References 46 publications

Susceptibility to Acute Mouse Adenovirus Type 1 Respiratory Infection and Establishment of Protective Immunity in Neonatal Mice

Susceptibility to Acute Mouse Adenovirus Type 1 Respiratory Infection and Establishment of Protective Immunity in Neonatal Mice

Rapid Proliferation and Differentiation Impairs the Development of Memory CD8+ T Cells in Early Life

Progress in understanding and controlling respiratory syncytial virus: Still crazy after all these years

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