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IMPACT OF REPEATED INFLUENZA VACCINATION AMONG CHILDREN AND ADULTS. Universal Vaccination Against Influenza- Are We Ready? Wendy A. Keitel, M.D. October 24, 2005. REPEATED IMMUNIZATION WITH INFLUENZA VIRUS VACCINES. QUESTIONS
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Universal Vaccination Against Influenza-
Are We Ready?
Wendy A. Keitel, M.D.
October 24, 2005
Consider live and inactivated vaccines
Original Antigenic Sin:
Preferential orientation of secondary antibodies toward priming epitopes
(Francis T, et al. Trans Assn Am Phys 66:231, 1953)
Annual vaccination of school children with inactivated influenza A vaccine confers no long-term advantage
(Hoskins TW, et al. Lancet i: 33, 1979)
The practice of offering annual revaccination
to adults seems open to question.
Most subjects were not vaccinated each year
‘First Vac’ group not present in all epidemics
Incomplete vaccination strategies preclude our ability to interpret data from 1975/6 epidemic
Vaccine potency unclear
Cohort effect possible
Authors excluded infected subjects from vaccinated groups
Effects of vaccination on illness severity not described‘THE HOSKIN’S PARADOX’Criticisms of Study Design
Beyer WEP et al. Vaccine 16:1929, 1998.
See Keitel WA. Semin Peditr Infect Dis 13:112, 2002.
From Gruber WC, et al. Am J Dis Child 144:595, 1990; Clover RD, et al. J Infect Dis 163:300, 1991; and Piedra PA and Glezen WP. Semin Pediatr Infect Dis 2(2):140, 1991.
Year 3: H3N2 Infection Rates
CR protected against illness
Adapted from Piedra PA and Glezen WP. Semin Pediatr Infect Dis 2(2):140, 1991.
Vaccine Group (N=52-82/group)
HAI Titer (log2) vs. A/Taiwan (H1N1)
Adapted from Gruber W, et al. J Infect Dis 169:241-7, 1994.
Percent with 1:40 Post (A/H3N2)
Note: Vaccine antigens differed from year to year
Year of Study
Adapted from Gross PA, et al. Vaccine 14:1280, 1996.
Cannot ascertain effects of repeated vaccination from the
Adapted from Neuzil K, et al. Pediatr Infect Dis J 20:733, 2001.
(2-A/H3N2, 1 Flu B)
Note: Influenza illnesses were milder in vaccinated children, and significant reductions in OM and LRD were noted
Adapted from Belshe RB, et al. NEJM 338:1405, 1998;
Belshe RB, et al. J Pediatr 136:168, 2000; and Longini IM, et al. Vaccine 18:1902, 2000.
Geometric Mean Titer
Did local immune responses inhibit vaccine virus replication?
Adapted from Bernstein DI, et al. Pediatr Infect Dis J 22:28, 2003.
See Piedra P et al. Pediatrics 116: e397, 2005.
(Rudenko LG, et al. J Infect Dis 168:881, 1993)
In most cases, infection rates were similar in FV and MV
Percent Protection vs. Placebo
Adapted from Keitel WA, et al. Am J Epidemiol 127:353, 1988; Vaccine 15:1114, 1997.
Percent of Subjects with Indicated Response
Adapted from Edwards KM, et al. J Infect Dis 169:68, 1994.
Relative Risk vs. Placebo (tan)
Logistic regression; OR (blue)
Adapted from Govaert TME, et al. JAMA 272:1661, 1994
% Reduction in Annual Mortality
(or per 195 revaccinations)
Adapted from Voordouw ACG, et al. JAMA 292:2089, 2004.
(Beyer WEP, et al. Arch Int Med 159:182, 1999)
Note: Several studies have shown that immune responses among elderly persons who were previously vaccinated were inferior to those immunized for the first time; however, groups were not randomized.
(Beyer WEP, et al. Vaccine 14:1331. 1996; Goodwin K, et al. Vaccine, Oct. 3 Epub; Keitel WA, et al. Manuscript in preparation).
Smith DJ et al. Proc Nat Acad Sci 96:14001, 1999
Munoz ET and Deem MW. Vaccine 23:1144, 2005.
Additional data are needed, including:
(Hoskins TW, et al. Lancet 1973; ii, 116)
(Hoskins TW, et al. Lancet 1976; i, 105)
(Hoskins TW, et al. Lancet 1979; i, 33
No single vaccination group was included,
and not all subjects in vaccinated groups
were vaccinated just prior to the epidemic.
Virus Year 1 Year 2___
H1N1 A/Texas A/Shenzhen
H3N2 A/Wuhan A/Wuhan
B B/Harbin B/Harbin
Geometric Mean Titer Post
Adapted from Belshe RB, et al. NEJM 338:1405, 1998; Belshe RB, et al. J Pediatr 136:168, 2000.