Original antigenic sin responses to influenza viruses.
ABSTRACT Most immune responses follow Burnet's rule in that Ag recruits specific lymphocytes from a large repertoire and induces them to proliferate and differentiate into effector cells. However, the phenomenon of "original antigenic sin" stands out as a paradox to Burnet's rule of B cell engagement. Humans, upon infection with a novel influenza strain, produce Abs against older viral strains at the expense of responses to novel, protective antigenic determinants. This exacerbates the severity of the current infection. This blind spot of the immune system and the redirection of responses to the "original Ag" rather than to novel epitopes were described fifty years ago. Recent reports have questioned the existence of this phenomenon. Hence, we revisited this issue to determine the extent to which original antigenic sin is induced by variant influenza viruses. Using two related strains of influenza A virus, we show that original antigenic sin leads to a significant decrease in development of protective immunity and recall responses to the second virus. In addition, we show that sequential infection of mice with two live influenza virus strains leads to almost exclusive Ab responses to the first viral strain, suggesting that original antigenic sin could be a potential strategy by which variant influenza viruses subvert the immune system.
- SourceAvailable from: Amesh A AdaljaEmerging Infectious Diseases 06/2010; 16(6):1028-9. · 6.79 Impact Factor
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ABSTRACT: We looked for evidence of antibodies to the 2009 influenza A/H1N1 pandemic virus in panels of sera from individuals living in metropolitan France, obtained either before, during or after the epidemic, using standard haemagglutination inhibition and microneutralization tests. The difference between seroprevalence values measured in post- and pre-epidemic panels was used as an estimate of seroconversion rate in different age groups (23.4% (0-24 years, age-group 0); 16.5% (25-34); 7.9% (35-44); 7.2% (45-54); 1.6% (55-64); and 3.1% (>65)), confirming that the distribution of cases in different age groups was similar to that of the seasonal H1N1 virus. During the pre-pandemic period low-titre cross-reactive antibodies were present in a large proportion of the population (presumably acquired against seasonal H1N1) whereas cross-reactive antibodies were detected in individuals over the age of 65 years with significantly higher prevalence and serological titres (presumably acquired previously against Spanish flu-related H1N1 strains). Clinical data and analysis of post-pandemic seroprevalence showed that few of these latter patients were infected by the influenza virus during the epidemic. In contrast, the majority of both clinical cases and seroconversions were recorded in the 0-24 age group and a global inverse relationship between prevalence of antibodies to pH1N1 in the pre-pandemic period and rate of seroconversion was observed amongst age groups. Our results emphasize the complex relationships involved in antigenic reactivity to pandemic and seasonal H1N1 viral antigens; hence the difficulty in distinguishing between low-titre specific and cross-reactive antibodies, establishing precise seroprevalence numbers and fully understanding the relationship between previous immunity to seasonal viruses and protection against the novel variant.Clinical Microbiology and Infection 04/2011; 18(2):177-83. · 4.58 Impact Factor
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ABSTRACT: Background. Recent studies suggest that influenza vaccination in the previous season may influence the effec-tiveness of current-season vaccination, but this has not been assessed in a single population over multiple years. Methods. Patients presenting with acute respiratory illness were prospectively enrolled during the 2004–2005 through 2012–2013 influenza seasons. Respiratory swabs were tested for influenza and vaccination dates obtained from a validated registry. Vaccination status was determined for the current, previous, and prior 5 seasons. Vaccine effectiveness (VE) was calculated for participants aged ≥9 years using logistic regression models with an interaction term for vaccination history. Results. There were 7315 enrollments during 8 seasons; 1056 (14%) and 650 (9%) were positive for influenza A (H3N2) and B, respectively. Vaccination during current only, previous only, or both seasons yielded similar protec-tion against H3N2 (adjusted VE range, 31%–36%) and B (52%–66%). In the analysis using 5 years of historical vac-cination data, current season VE against H3N2 was significantly higher among vaccinated individuals with no prior vaccination history (65%; 95% confidence interval [CI], 36%–80%) compared with vaccinated individuals with a frequent vaccination history (24%; 95% CI, 3%–41%; P = .01). VE against B was 75% (95% CI, 50%–87%) and 48% (95% CI, 29%–62%), respectively (P = .05). Similar findings were observed when analysis was restricted to adults 18–49 years. Conclusions. Current-and previous-season vaccination generated similar levels of protection, and vaccine-induced protection was greatest for individuals not vaccinated during the prior 5 years. Additional studies are needed to understand the long-term effects of annual vaccination. Keywords. influenza; vaccine effectiveness. The Advisory Committee on Immunization Practices (ACIP) has recommended annual influenza vaccina-tions for all persons aged ≥6 months since 2010 . Although annual vaccination has been recommended for adults aged ≥65 years and certain high-risk groups for decades, the impact of prior vaccination history on current-season vaccine effectiveness (VE) is unclear. Despite previous debates on the relevance of repeated vaccination [2, 3], few influenza VE studies have consid-ered the effect of vaccinations received in prior seasons. In the 1980s, a multiseason randomized, placebo-controlled trial among healthy adults found no con-sistent differences in efficacy of primary vs repeated vaccination against serologically confirmed influenza [4, 5]. Recent observational studies have suggested that VE may be influenced by prior season vaccination [6–12]. However, these studies were limited to 1 or 2 seasons,Clinical Infectious Diseases 09/2014; 54449. · 9.37 Impact Factor