1690. The Development of the Immune System in Early Life and its Response to Vaccination: A System Analysis Approach.
Session: Oral Abstract Session: Vaccines in the Young and Vulnerable
Friday, October 28, 2016: 3:15 PM
Room: 388-390
Background: Immune responses to vaccines in infants are generally less protective than in older individuals. However, the mechanisms responsible for these inefficient responses are poorly defined. Our previous studies showed that baseline expression of innate immune genes is markedly suppressed in infants < 6 mo of age.

Objective: To define changes in cellular and transcriptional immune profiles induced by routine vaccinations in infants.  

Methods: We evaluated 47 healthy infants during routine vaccinations: 2 mo (n=24), 6 mo (n=16) and 12mo (n=7). Peripheral blood was collected on day (d) 0 (pre-vaccination), d7 and d30 post-vaccination for analysis of: a) immune cell populations by flow cytometry and b) immune genes transcriptome with microarrays.

Results: Flow: In 2 mo there was a significant increase on d7 of absolute numbers of monocytes; p<0.05, and on d30 of total, naïve and transitional B cells, and plasma cells, as well as T follicular helper (Tfh) cells and subsets (Tfh1, Tfh2 and Tfh17); p<0.01. In 12 mo on d30 we observed significant increases in memory B cells, plasmablasts, and Tfh cells and subsets; p<0.01. Transcriptome: In 2 mo on d7 post-vaccination there were 339 significantly (Man-Whitney; p<0.05) overexpressed genes (interferon, inflammation, monocytes and plasma cells), while on d30 there were 111 significantly overexpressed genes (inflammation and B cells). In 6 mo there were only 24 significantly overexpressed genes (interferon) at d7 post-vaccination. In 12 mo, there were 143 significantly overexpressed genes on d7 (interferon, inflammation and monocytes), and 15 overexpressed genes (cytotoxic/natural killer cells) on d30. We observed significant correlations in 2 mo on d7 between plasma cell genes and increase in Tfh1 cells (p=0.01; r=0.62), and between inflammation genes and increases in neutrophils (p=0.04; r=0.73) and monocytes (p<0.01; r=0.68).

Conclusion: 2 mo infants demonstrated a robust cellular and transcriptional immune response after vaccination. While 6 and 12 mo infants also showed significant overexpression of immune–related genes after vaccination, their responses were less significant, suggesting age-dependent differences likely related to the development of the immune system early in life.

Raquel Giacomelli Cao, MD PhD1, Eleonora Bunsow, MD PhD1, Bennet Smith, BS1, Santtu Heinonen, MD, PhD2, Sara Mertz, BS1, Fang Ye, PhD1, Victoria Best, PhD1, Asuncion Mejias, MD, PhD3 and Octavio Ramilo, MD, FPIDS4,5, (1)Center for Vaccines & Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, (2)Children's Hospital, Helsinki University Central Hospital, Helsinki, Finland, (3)Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, Columbus, OH, (4)Pediatrics, Section of Infectious Diseases, Nationwide Children's Hospital, Columbus, OH, (5)Center for Vaccines & Immunity, The Research Institute At Nationwide Children's Hospital, Columbus, OH

Disclosures:

R. Giacomelli Cao, None

E. Bunsow, None

B. Smith, None

S. Heinonen, None

S. Mertz, None

F. Ye, None

V. Best, None

A. Mejias, Janssen: Grant Investigator and Scientific Advisor , Consulting fee and Research grant
Alios: Consultant , Consulting fee
Abbvie: CME lecture , Speaker honorarium
Novartis: CME lecture , Speaker honorarium
Gilead: Grant Investigator , Grant recipient

O. Ramilo, Abbvie: Consultant and Scientific Advisor , Consulting fee and Speaker honorarium
Medimmune: Scientific Advisor , Consulting fee
Janssen: Consultant , Investigator and Scientific Advisor , Consulting fee and Research grant
HuMabs: Scientific Advisor , Consulting fee
Regeneron: Scientific Advisor , Consulting fee

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