Abstract:This review discusses factors and strategies that must be considered and addressed during immunogenicity assessments of pandemic influenza vaccines, which may provide useful information for future influenza pandemics.
“…1). Although many studies have examined the relationship between vaccination and antibody responses 12–14 , very few have examined the relationship between viral kinetics and antibody responses in animals 15–17 or humans 18 , or the effects of previous infection history on antibody responses 19–22 .Figure 1Behaviour of virus, the patient’s immune response to infection, and household transmission are considered to be inter-related in influenza studies. This study is focused on the relationship between patients’ immune response and the immunological factors that may contribute to this response (Relationship-1) and the relationship between patients’ immune response and virus dynamics (Relationship-2).…”
Neuraminidase inhibitors (NAIs) complement influenza virus infection management by helping to clear virus, alleviate symptoms, and reduce transmission. In a previous randomised study, we examined the effect of 4 NAIs on virus clearance and influenza symptoms in Japanese paediatric patients. In this second analysis, we examined the effects of NAI treatment on antibody responses and virus clearance, and the relationships between antibody responses and patients’ infection histories (previous infection; asymptomatic infection via household members of same virus type/subtype; vaccination), and between infection histories and viral kinetics. Haemagglutination inhibition (HI) antibody responses produced HI titres ≥40 by Day 14 of NAI treatment, in parallel with virus clearance (trend test
P
= 0.001). Comparing patients with and without influenza infection histories (directly or asymptomatic infection via household members) showed that infection history had a marked positive effect on HI antibody responses in patients vaccinated before the current influenza season (before enrolment). Current virus clearance was significantly faster in patients previously infected with the same virus type/subtype than in those not previously infected, and clearance pattern depended on the NAI. Assessment of anti-influenza effects of antiviral drugs and vaccines should consider virus and antibody dynamics in response to vaccination and natural infection histories.
“…1). Although many studies have examined the relationship between vaccination and antibody responses 12–14 , very few have examined the relationship between viral kinetics and antibody responses in animals 15–17 or humans 18 , or the effects of previous infection history on antibody responses 19–22 .Figure 1Behaviour of virus, the patient’s immune response to infection, and household transmission are considered to be inter-related in influenza studies. This study is focused on the relationship between patients’ immune response and the immunological factors that may contribute to this response (Relationship-1) and the relationship between patients’ immune response and virus dynamics (Relationship-2).…”
Neuraminidase inhibitors (NAIs) complement influenza virus infection management by helping to clear virus, alleviate symptoms, and reduce transmission. In a previous randomised study, we examined the effect of 4 NAIs on virus clearance and influenza symptoms in Japanese paediatric patients. In this second analysis, we examined the effects of NAI treatment on antibody responses and virus clearance, and the relationships between antibody responses and patients’ infection histories (previous infection; asymptomatic infection via household members of same virus type/subtype; vaccination), and between infection histories and viral kinetics. Haemagglutination inhibition (HI) antibody responses produced HI titres ≥40 by Day 14 of NAI treatment, in parallel with virus clearance (trend test
P
= 0.001). Comparing patients with and without influenza infection histories (directly or asymptomatic infection via household members) showed that infection history had a marked positive effect on HI antibody responses in patients vaccinated before the current influenza season (before enrolment). Current virus clearance was significantly faster in patients previously infected with the same virus type/subtype than in those not previously infected, and clearance pattern depended on the NAI. Assessment of anti-influenza effects of antiviral drugs and vaccines should consider virus and antibody dynamics in response to vaccination and natural infection histories.
“…S1 ), suggesting strong natural exposure. An inverse association between pre-vaccination titre and vaccine response has been reported in studies of other vaccines, such as influenza and respiratory syncytial virus vaccines, and oral cholera vaccines [31] , [32] , [33] . Also, it is clear from individual subject listings that the immune response against UspA2 was highly variable (data not shown).…”
“…The WHO guide to vaccinations note that while pneumococcal polysaccharide vaccines induce an initial rise in antibody levels, these levels decline in older adults to pre‐vaccination levels after 4‐7 years . Many studies have shown that seasonal influenza antibodies may persist up to 4 years …”
Hypogammaglobulinemia (HGG) frequently occurs in recipients after types of (SOT). The incidence and significance of HGG in HIV+ recipients of SOT are just being explored. We reported that 12% of the recipients in the SOT in multi‐center HIV‐TR (HIV‐TR) Study developed moderate or severe HGG at 1 year. In LT recipients, this was associated with serious infections and death. We have now further characterized the decreased antibodies in HIV+ SOT recipients who developed HGG. We measured the levels of pathogen‐specific antibodies and poly‐specific self‐reactive antibodies (PSA) in relation to total IgG levels from serial serum samples for 20 HIV+ SOT recipients who developed moderate to severe HGG following SOT. Serum antibody levels to measles, tetanus toxoid, and HIV‐1 were determined by EIA. Levels of PSAs were determined by incubating control lymphocytes with patient serum, staining with anti‐human IgG Fab‐FITC, and analysis by flow cytometry. Levels of PSA were higher compared to healthy, HIV‐uninfected controls at pre‐transplant baseline and increased by weeks 12 and 26, but the changes were not significant. Likewise, anti‐HIV antibody levels remained unchanged over time. In contrast, antibody levels against measles and tetanus were significantly reduced from baseline by week 12, and did not return to baseline, even after 2 years. For HIV patients who develop moderate to severe HGG after transplant, the reduction in IgG levels is associated with a significant decrease in pathogen‐specific antibody titers, while PSA levels and anti‐HIV antibodies are unchanged. This may contribute to infectious complications and other clinical endpoints.
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