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Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children.

ABSTRACT: Two doses of either trivalent live attenuated or inactivated influenza vaccines (LAIV and TIV, respectively) are approved for young children (? 24 months old for LAIV and ? 6 months old for TIV) and induce protective antibody responses. However, whether combinations of LAIV and TIV are safe and equally immunogenic is unknown. Furthermore, LAIV is more protective than TIV in children for unclear reasons.Children 6-35 months old were administered, 1 month apart, 2 doses of either TIV or LAIV, or combinations of LAIV and TIV in both prime/boost sequences. Influenza-specific antibodies were measured by hemagglutination inhibition (HAI), and T cells were studied in flow cytometric and functional assays. Highly conserved M1, M2, and NP peptides predicted to be presented by common HLA class I and II were used to stimulate interferon-? enzyme-linked immunospot responses.All LAIV and/or TIV combinations were well tolerated and induced similar HAI responses. In contrast, only regimens containing LAIV induced influenza-specific CD4(+), CD8(+), and ?? T cells, including T cells specific for highly conserved influenza peptides.Prime/boost combinations of LAIV and TIV in young children were safe and induced similar protective antibodies. Only LAIV induced CD4(+), CD8(+), and ?? T cells relevant for broadly protective heterosubtypic immunity.NCT00231907.

SUBMITTER: Hoft DF

PROVIDER: S-EPMC3156924 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children.

Hoft Daniel F DF Babusis Elizabeth E Worku Shewangizaw S Spencer Charles T CT Lottenbach Kathleen K Truscott Steven M SM Abate Getahun G Sakala Isaac G IG Edwards Kathryn M KM Creech C Buddy CB Gerber Michael A MA Bernstein David I DI Newman Frances F Graham Irene I Anderson Edwin L EL Belshe Robert B RB

The Journal of infectious diseases 20110815 6

<h4>Background</h4>Two doses of either trivalent live attenuated or inactivated influenza vaccines (LAIV and TIV, respectively) are approved for young children (≥ 24 months old for LAIV and ≥ 6 months old for TIV) and induce protective antibody responses. However, whether combinations of LAIV and TIV are safe and equally immunogenic is unknown. Furthermore, LAIV is more protective than TIV in children for unclear reasons.<h4>Methods</h4>Children 6-35 months old were administered, 1 month apart, ...[more]

PMID: 21846636

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Project description:LAIV and TIV are effective for prevention of influenza infection in children, but the mechanisms associated with protection are still not well defined. We analyzed the differences in B cell responses and transcriptional profiles. Compared to baseline, LAIV elicited a significant increase in naM-CM-/ve, memory and transitional B cells on day 30, while vaccination with TIV elicited an increase in number of plasmablasts on day 7. Antibody titers against the three vaccine strains (H1N1, H3N2 and B) were significantly higher in the TIV group and correlated with number of antibody-secreting cells. Regarding transcriptional profiles, both vaccines induced expression of interferon signaling, but at different time points, TIV on 1 day, and LAIV on day 7 day post-vaccination, the last only in children younger than 5 years old. Interferon-related genes over expressed in both vaccinated groups correlated with antibody titers of H3N2 vaccines strain. These results suggest that LAIV and TIV induced significant different B cell responses in vaccinated children. Early induction on interferon genes appears important for development of effective antibody responses. Longitudinal study with time points at baseline (day 0), 24hr, day 7 and day 30. 136 total samples analyzed. This was a prospective cohort of previously healthy children 6 months to 14 years of age enrolled between October 2011 and February 2012. Thirty seven subjects were randomized to receive one dose of either LAIV (FluMistM-BM-., MedImmune) (n= 20) or TIV (FluzoneM-BM-., Sanofi Pasteur) (n= 17). Two exceptions were applied to the randomization: four children with ages between 6 months and 2 years old received TIV, since LAIV is not licensed on this age group, and four children with controlled asthma also received TIV following CDCM-bM-^@M-^Ys recommendations. One child aged 6 months at the time of enrollment received two doses of the vaccine with one month interval apart, since it was his first influenza vaccination. Exclusion criteria included any medical comorbidities or chronic conditions (lung, kidney or heart disease), use of systemic steroids in the previous 2 weeks, and congenital or acquired immunodeficiencies. The 2011-2012 LAIV and TIV vaccines contained A/California/7/2009 (H1N1)-like, A/Perth/16/2009 (H3N2)-like and B/Brisbane/60/2008-like antigens, the same strains used on the 2010-2011 influenza vaccine. TIV recipients aged 6 to 35 months old received 0.25 mL intramuscularly and recipients aged 36 months and older received 0.5 mL. LAIV recipients received 0.2 mL by intranasal route, 0.1 mL per nostril. Blood samples were collected at four time points, on day zero prior to vaccination, and day 1, day 7 (range 6-8) and day 30 (range 27-33) post-vaccination.

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Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children.

Publications

Live and inactivated influenza vaccines induce similar humoral responses, but only live vaccines induce diverse T-cell responses in young children.

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