Dataset Information

Antibodies in lymphocyte supernatants can distinguish between neutralising antibodies induced by RSV vaccination and pre-existing antibodies induced by natural infection.

ABSTRACT:

Introduction

Respiratory syncytial virus (RSV) is the single most important cause of severe respiratory illness in infants. There is no effective vaccine and the only effective treatment available is the monoclonal antibody palivizumab which reduces the risk of severe RSV disease in prematurely born infants. However, palivizumab is too costly to allow for wide implementation and thus treatment is restricted to supportive care. Despite extensive efforts to develop a vaccine, progress has been hindered by the difficulty in measuring and assessing immunological correlates of RSV vaccine efficacy in the presence of high levels of pre-existing RSV antibodies.

Methods

Here we describe a new method for measuring the functional activity of antibodies induced by vaccination distinct from pre-existing antibodies. Antibodies in lymphocyte supernatants (ALS) from the cultured peripheral blood mononuclear cells (PBMCs) of young adults who had recently been vaccinated with a novel RSV candidate vaccine were directly assayed for virus neutralising activity. An ELISA method was used to measure antibodies in nasal and serum samples and then compared with the adapted ALS based method.

Results

There was a wide background distribution of RSV-specific antibodies in serum and nasal samples that obscured vaccine-specific responses measured two weeks after vaccination. No RSV-specific antibodies were observed at baseline in ALS samples, but a clear vaccine-specific antibody response was observed in ALS seven days after the administration of each dose of vaccine. These vaccine-specific antibodies in ALS displayed functional activity in vitro, and quantification of this functional activity was unperturbed by pre-existing antibodies from natural exposure. The results demonstrate a promising new approach for assessing functional immune responses attributed to RSV vaccines.

SUBMITTER: Gerretsen HE

PROVIDER: S-EPMC7116660 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Publications

Antibodies in lymphocyte supernatants can distinguish between neutralising antibodies induced by RSV vaccination and pre-existing antibodies induced by natural infection.

Gerretsen Hannah E HE Capone Stefania S Vitelli Alessandra A Reyes Laura S LS Thompson Amber A Jones Claire C Green Christopher A CA Pollard Andrew J AJ Sande Charles J CJ

Vaccine 20181011 46

<h4>Introduction</h4>Respiratory syncytial virus (RSV) is the single most important cause of severe respiratory illness in infants. There is no effective vaccine and the only effective treatment available is the monoclonal antibody palivizumab which reduces the risk of severe RSV disease in prematurely born infants. However, palivizumab is too costly to allow for wide implementation and thus treatment is restricted to supportive care. Despite extensive efforts to develop a vaccine, progress has ...[more]

PMID: 30318168

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Project description:BackgroundThe Step trial raised the possibility that uncircumcised men with pre-existing Ad5 neutralizing antibodies carried an increased risk of HIV infection after vaccination. Thus, understanding Ad seropositivity in humans is important to the development of an AIDS vaccine. Here, we analyze the impact of different Ad5-specific neutralizing antibodies on immune function and clinical outcome.Methods and findingsAd seropositivity in the Step trial volunteers was analyzed using chimeric rAd5/35 vectors to characterize their specificity for Ad5 fiber and non-fiber external (capsid) proteins. Immune responses and HIV seropositivity were correlated with the specificity of Ad5-neutralizing antibodies. Neutralizing antibodies induced by the vaccine in Ad5 seronegative subjects were directed preferentially to Ad5 capsid proteins, although some fiber-neutralizing antibodies could be detected. Pre-vaccination Ad5 serostatus did not affect the capsid-directed response after three vaccinations. In contrast, anti-fiber antibody titers were significantly higher in volunteers who were Ad5 seropositive prior to vaccination. Those Ad5 seropositive subjects who generated anti-capsid responses showed a marked reduction in vaccine-induced CD8 responses. Unexpectedly, anti-vector immunity differed qualitatively in Ad5 seropositive participants who became HIV-1 infected compared to uninfected case controls; Ad5 seropositive participants who later acquired HIV had lower neutralizing antibodies to capsid. Moreover, Ad35 seropositivity was decreased in HIV-infected subjects compared with uninfected case controls, while seroprevalence for other serotypes including Ad14, Ad28 and Ad41 was similar in both groups.ConclusionsTogether, these findings suggest that the case subjects were less immunologically responsive prior to infection. Subjects infected during the Step trial had qualitative differences in immunity that increased their risk of HIV-1 infection independent of vaccination.

Dataset Information

Antibodies in lymphocyte supernatants can distinguish between neutralising antibodies induced by RSV vaccination and pre-existing antibodies induced by natural infection.

Introduction

Methods

Results

Publications

Antibodies in lymphocyte supernatants can distinguish between neutralising antibodies induced by RSV vaccination and pre-existing antibodies induced by natural infection.

Similar Datasets

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