The Doctrine of Original Antigenic Sin: Separating Good From Evil

Monto, Arnold S.; Malosh, Ryan E.; Petrie, Joshua G.; Martin, Emily T.

doi:10.1093/infdis/jix173

Cited by 152 publications

(158 citation statements)

References 50 publications

(53 reference statements)

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“…imprints on the immune memory the antigenic type of the infecting influenza virus. 13 This first infection may differentially imprint an antibody repertoire that can later effect immune responses to subsequent influenza virus exposures. [13][14][15] Most studies on imprinting have focused on IAV viruses, but this condition most likely also occurs during IBV infections.…”

Section: Discussionmentioning

confidence: 99%

“…13 This first infection may differentially imprint an antibody repertoire that can later effect immune responses to subsequent influenza virus exposures. [13][14][15] Most studies on imprinting have focused on IAV viruses, but this condition most likely also occurs during IBV infections. It is not currently well understood if high HAI titers to a specific IBV lineage reflects the dominate circulating IBV strains at the time of first IBV infection.…”

Section: Discussionmentioning

confidence: 99%

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Impact of age and pre-existing immunity on the induction of human antibody responses against influenza B viruses

Carlock

Ingram

Clutter

et al. 2019

Human Vaccines & Immunotherapeutics

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Pre-existing immunity to influenza is dependent on a number of factors and can vary greatly within and across influenza subtypes. In this study, volunteers (aged 18–85 years) were vaccinated with split, inactivated FluzoneTM in four consecutive influenza seasons from 2013 to 2016. The impact of repeat vaccination on breadth and durability of functional antibodies was assessed for total IgG and IgA anti-hemagglutinin (HA) binding antibodies and hemagglutination-inhibition (HAI) activity against both influenza B lineages. Many subjects were able to maintain high seroprotective titers to the vaccine strains in subsequent years, which resulted in low vaccine-induced seroconversion rates. This was especially evident in younger subjects who typically had higher titers and maintained these titers into the following season. In contrast, the HAI titers in elderly subjects were generally lower and more likely to decline prior to the start of the next influenza season. Immunological recall or ‘back-boosting’ to antigenically related viruses was associated with seroconversion. Overall, influenza vaccination in both younger and older people elicited broadly reactive immune responses within a lineage, as well as cross-reactive immune responses between lineages. This study exemplified the impact that age and influenza exposure history have on determining an individual’s ability to respond to future influenza infections.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Impact of age and pre-existing immunity on the induction of human antibody responses against influenza B viruses

Carlock

Ingram

Clutter

et al. 2019

Human Vaccines & Immunotherapeutics

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“…We demonstrate that the magnitude of the response to B/Phuket in the whole cohort is approximately twofold lower than the two FluA components, and is reflected in both the seroprotection and seroconversion rates. The reason for this is unclear, but may result from the original antigenic sin hypothesis, where exposure to different circulating viral strains that prime the immune system during childhood which may then go on to determine which response is able to be boosted by the vaccine [28]. While the high level of pre-existing seroprotection to A/H1N1 in all groups is probably a result of the inclusion of the same components in both the 2014 and 2015 TIV, the other differences between the groups are harder to reconcile.…”

Section: Discussionmentioning

confidence: 99%

“…For example, the young controls appeared to respond less well to the A/H3N2 components than either the COPD or age-matched controls. The reason for this is unclear, but may result from the original antigenic sin hypothesis, where exposure to different circulating viral strains that prime the immune system during childhood which may then go on to determine which response is able to be boosted by the vaccine [28]. Thus, the A/H3N2 may have been more dominant during the maturation of the immune response in the older volunteers, whereas A/H1N1 may have been more dominant at the time of immune maturation in the young volunteers.…”

Section: Discussionmentioning

confidence: 99%

Acquired immune responses to the seasonal trivalent influenza vaccination in COPD

Staples

Williams

Bonduelle

et al. 2019

Clinical and Experimental Immunology

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Summary Epidemiological data suggest that influenza vaccination protects against all‐cause mortality in chronic obstructive pulmonary disease (COPD) patients. However, recent work has suggested there is a defect in the ability of some COPD patients to mount an adequate humoral response to influenza vaccination. The aim of our study was to investigate humoral and cell‐mediated vaccine responses to the seasonal trivalent influenza vaccination (TIV) in COPD subjects and healthy controls. Forty‐seven subjects were enrolled into the study; 23 COPD patients, 13 age‐matched healthy controls (HC ≥ 50) and 11 young healthy control subjects (YC ≤ 40). Serum and peripheral blood mononuclear cells (PBMC) were isolated pre‐TIV vaccination and at days 7 and 28 and 6 months post‐vaccine for haemagglutinin inhibition (HAI) titre, antigen‐specific T cell and antibody‐secreting cell analysis. The kinetics of the vaccine response were similar between YC, HC and COPD patients and there was no significant difference in antibody titres between these groups at 28 days post‐vaccine. As we observed no disease‐dependent differences in either humoral or cellular responses, we investigated if there was any association of these measures with age. H1N1 (r = −0·4253, P = 0·0036) and influenza B (r = −0·344, P = 0·0192) antibody titre at 28 days negatively correlated with age, as did H1N1‐specific CD4+ T helper cells (r = −0·4276, P = 0·0034). These results suggest that age is the primary determinant of response to trivalent vaccine and that COPD is not a driver of deficient responses per se. These data support the continued use of the yearly trivalent vaccine as an adjunct to COPD disease management.

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“…17 This was the first time in the recent era that such a reduction was documented, thus continuing historical debates on whether repeat vaccination resulted in reduced protection. [27][28][29][30] These original findings of a repeat vaccination effect prompted a furthering of the hypothesis that antibody response to vaccination was decreased after multiple annual administration of vaccines of similar antigenic make-up.…”

Section: Influenza Vaccine Effectiveness and Effect Of Prior Vaccinationmentioning

confidence: 99%

Data resource profile: Household Influenza Vaccine Evaluation (HIVE) Study

Monto

Malosh

Evans

et al. 2019

International Journal of Epidemiology

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Acute respiratory infections (ARI) are a major cause of morbidity worldwide. 1 Some of the earliest studies to describe the epidemiology of these infections were household cohort studies. [2][3][4][5][6][7] The largest of these were conducted in Seattle, Washington and Tecumseh, Michigan in the 1960s and 1970s 6,7 and they provided information on the relative frequency, seasonality and symptomatic characteristics of ARI shortly after many respiratory viruses were first identified. 7 Given that the role of household structure in seasonal incidence and transmission of respiratory viruses was the primary objective, an individual's longitudinal history of infection was not a major focus. Indeed, during the first phase of the Tecumseh Study of Respiratory Illness, households were maintained on report for only 1 year, and then gradually replaced so that the entire community could be represented over time. 8 These historical studies relied on cell culture for virus identification, a method that requires specimens to be processed quickly and is considerably less sensitive than current molecular methods. 9 For this reason, the Tecumseh study and others relied extensively on serodiagnosis of influenza infection using twice yearly blood specimens. 10 It was not possible to time infections in those who only were serologically positive, limiting the ability to do robust analyses of transmission patterns. 11 With current molecular techniques, it has become much easier to identify a broad range of agents of respiratory infection. This allows documentation of infection, co-infection and subsequent re-infection. Collecting specimens within a short time from the onset of symptoms still maximizes the likelihood of accurate and timely identification of viruses associated with a respiratory illness for studies of transmission and vaccine effectiveness. Collection of regular blood specimens continues to be valuable as well, for both virus identification and for analysis of serologic correlates of protection.The Household Influenza Vaccine Evaluation (HIVE) Study is an ongoing prospective household cohort study that began in 2010. The HIVE Study was based on the original Tecumseh Study of Respiratory Illness 6 with several key modifications to illness surveillance and to laboratory methods for identification of respiratory viruses. While respiratory virus infections in general could be studied, the primary objective was to estimate the effectiveness of influenza vaccines using a cohort design for comparison with studies using the testnegative design (TND). Under the TND, specimens are collected from participants who meet a respiratory illness case V C The Author(s)

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The Doctrine of Original Antigenic Sin: Separating Good From Evil

Cited by 152 publications

References 50 publications

Impact of age and pre-existing immunity on the induction of human antibody responses against influenza B viruses

Impact of age and pre-existing immunity on the induction of human antibody responses against influenza B viruses

Acquired immune responses to the seasonal trivalent influenza vaccination in COPD

Data resource profile: Household Influenza Vaccine Evaluation (HIVE) Study

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