Dataset Information

Original Antigenic Sin Shapes the Immunological Repertoire Evoked by Human Cytomegalovirus Glycoprotein B/MF59 Vaccine in Seropositive Recipients.

ABSTRACT: A human cytomegalovirus (HCMV) vaccine is urgently needed to protect against primary infection and enhance existing immunity in HCMV-infected individuals (HCMV+). Using sera from HCMV+ glycoprotein B/MF59 vaccine recipients prior to transplant, we investigated the composition of the immune response. Vaccination boosted preexisting humoral responses in our HCMV+ cohort but did not promote de novo responses against novel linear epitopes. This suggests that prior natural infection has a profound effect on shaping the antibody repertoire and subsequent response to vaccination ("original antigenic sin"). Thus, vaccination of HCMV+ may require strategies of epitope presentation distinct from those intended to prevent primary infection.

SUBMITTER: Baraniak I

PROVIDER: S-EPMC6581893 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Original Antigenic Sin Shapes the Immunological Repertoire Evoked by Human Cytomegalovirus Glycoprotein B/MF59 Vaccine in Seropositive Recipients.

Baraniak Ilona I Kern Florian F Holenya Pavlo P Griffiths Paul P Reeves Matthew M

The Journal of infectious diseases 20190601 2

A human cytomegalovirus (HCMV) vaccine is urgently needed to protect against primary infection and enhance existing immunity in HCMV-infected individuals (HCMV+). Using sera from HCMV+ glycoprotein B/MF59 vaccine recipients prior to transplant, we investigated the composition of the immune response. Vaccination boosted preexisting humoral responses in our HCMV+ cohort but did not promote de novo responses against novel linear epitopes. This suggests that prior natural infection has a profound ef ...[more]

PMID: 30815685

Similar Datasets

Project description:BackgroundA pandemic novel H1N1 swine-origin influenza virus has emerged. Most recently the World Health Organization has announced that in a country-dependent fashion, up to 15% of cases may require hospitalization, often including respiratory support. It is now clear that healthy children and young adults are disproportionately affected, most unusually among those with severe respiratory disease without underlying conditions. One possible explanation for this case age distribution is the doctrine of Original Antigenic Sin, i.e., novel H1N1 may be antigenically similar to H1N1 viruses that circulated at an earlier time. Persons whose first exposure to influenza viruses was to such similar viruses would be relatively immune. However, this principle is not sufficient to explain the graded susceptibility between ages 20 and 60, the reduced susceptibility in children below age 10, and the unusual toxicity observed.MethodsWe collected case data from 11 countries, about 60% of all cases reported through mid-July 2009. We compared sequence data for the hemagglutinin of novel H1N1 with sequences of H1N1 viruses from 1918 to the present. We searched for sequence differences that imply loss of antigenicity either directly through amino acid substitution or by the appearance of sites for potential glycosylation proximal to sites known to be antigenic in humans. We also considered T-cell epitopes.ResultsIn our composite, over 75% of confirmed cases of novel H1N1 occurred in persons < or = 30 years old, with peak incidence in the age range 10-19 years. Less than 3% of cases occurred in persons over 65, with a gradation in incidence between ages 20 and 60 years.The sequence data indicates that novel H1N1 is most similar to H1N1 viruses that circulated before 1943. Novel H1N1 lacks glycosylation sites on the globular head of hemagglutinin (HA1) near antigenic regions, a pattern shared with the 1918 pandemic strain and H1N1 viruses that circulated until the early 1940s. Later H1N1 viruses progressively added new glycosylation sites likely to shield antigenic epitopes, while T-cell epitopes were relatively unchanged.ConclusionsIn this evolutionary context, Original Antigenic Sin exposure should produce an immune response increasingly mismatched to novel H1N1 in progressively younger persons. We suggest that it is this mismatch that produces both the gradation in susceptibility and the unusual toxicity. Several murine studies suggest specific cell types as a likely basis of the unusual toxicity. These studies also point to widely available pharmaceutical agents as plausible candidates for mitigating the toxic effects. The principle of Original Antigenic Sin modified by glycosylation appears to explain both the case age distribution and the unusual toxicity pattern of the novel H1N1 pandemic. In addition, it suggests pharmaceutical agents for immediate investigation for mitigation potential, and provides strategic guidance for the distribution of pandemic mitigation resources of all types.

Dataset Information

Original Antigenic Sin Shapes the Immunological Repertoire Evoked by Human Cytomegalovirus Glycoprotein B/MF59 Vaccine in Seropositive Recipients.

Publications

Original Antigenic Sin Shapes the Immunological Repertoire Evoked by Human Cytomegalovirus Glycoprotein B/MF59 Vaccine in Seropositive Recipients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure