TY - JOUR
T1 - Higher PIK3C2B gene expression of H1N1+ specific B-cells is associated with lower H1N1 immunogenicity after trivalent influenza vaccination in HIV infected children
AU - Cotugno, Nicola
AU - Zicari, Sonia
AU - Morrocchi, Elena
AU - de Armas, Lesley R.
AU - Pallikkuth, Suresh
AU - Rinaldi, Stefano
AU - Ruggiero, Alessandra
AU - Manno, Emma Concetta
AU - Zangari, Paola
AU - Chiriaco, Maria
AU - Bernardi, Stefania
AU - Andrews, Sarah F.
AU - Cagigi, Alberto
AU - Rossi, Paolo
AU - McDermott, Adrian B.
AU - Pahwa, Savita
AU - Palma, Paolo
N1 - Funding Information:
This work was made possible by the support from a pilot award to NC from Miami Center for AIDS Research (CFAR), grants obtained by Bambino Ges? Children's Hospital (Ricerca corrente 2020 to NC), Associazione Volontari Bambino Ges?, Ricerca Finalizzata 2010, Ministero della Salute (RF_2010_2310438), and grants AI108472 and AI127347 to SP and the Laboratory Sciences Core of the Miami CFAR (P30AI073961) from the National Institutes of Health (NIH), which is supported by the following NIH Co-Funding and Participating Institutes and Centers: NIAID, NCI, NICHD, NHLBI, NIDA, NIMH, NIA, NIDDK, NIGMS, FIC, and OAR.
Funding Information:
This work was made possible by the support from a pilot award to NC from Miami Center for AIDS Research (CFAR), grants obtained by Bambino Gesú Children's Hospital (Ricerca corrente 2020 to NC), Associazione Volontari Bambino Gesù , Ricerca Finalizzata 2010, Ministero della Salute (RF_2010_2310438), and grants AI108472 and AI127347 to SP and the Laboratory Sciences Core of the Miami CFAR (P30AI073961) from the National Institutes of Health (NIH), which is supported by the following NIH Co-Funding and Participating Institutes and Centers: NIAID , NCI , NICHD , NHLBI , NIDA , NIMH , NIA , NIDDK , NIGMS , FIC , and OAR .
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/6
Y1 - 2020/6
N2 - Perinatally HIV-infected children (PHIV), despite successful antiretroviral therapy, present suboptimal responses to vaccinations compared to healthy-controls (HC). Here we investigated phenotypic and transcriptional signatures of H1N1-specific B-cells (H1N1-Sp) in PHIV, differentially responding to trivalent-influenza-vaccine (TIV), and HC. Patients were categorized in responders (R) and non-responders (NR) according to hemagglutination-inhibition-assay at baseline and 21 days after TIV. No differences in H1N1-Sp frequencies were found between groups. H1N1-Sp transcriptional analysis revealed a distinct signature between PHIV and HC. NR presented higher PIK3C2B and NOD2 expression compared to R, confirmed by downregulation of PIK3C2B in resting-memory of R after H1N1 in-vitro stimulation. In conclusion this study confirms that qualitative rather than quantitative analyses are needed to characterize immune responses in PHIV. These results further suggest that higher PIK3C2B in H1N1-Sp of NR is associated with lower H1N1 immunogenicity and may be targeted by future modulating strategies to improve TIV responses in PHIV.
AB - Perinatally HIV-infected children (PHIV), despite successful antiretroviral therapy, present suboptimal responses to vaccinations compared to healthy-controls (HC). Here we investigated phenotypic and transcriptional signatures of H1N1-specific B-cells (H1N1-Sp) in PHIV, differentially responding to trivalent-influenza-vaccine (TIV), and HC. Patients were categorized in responders (R) and non-responders (NR) according to hemagglutination-inhibition-assay at baseline and 21 days after TIV. No differences in H1N1-Sp frequencies were found between groups. H1N1-Sp transcriptional analysis revealed a distinct signature between PHIV and HC. NR presented higher PIK3C2B and NOD2 expression compared to R, confirmed by downregulation of PIK3C2B in resting-memory of R after H1N1 in-vitro stimulation. In conclusion this study confirms that qualitative rather than quantitative analyses are needed to characterize immune responses in PHIV. These results further suggest that higher PIK3C2B in H1N1-Sp of NR is associated with lower H1N1 immunogenicity and may be targeted by future modulating strategies to improve TIV responses in PHIV.
KW - Antigen specific B cells
KW - Gene expression
KW - H1N1
KW - Influenza vaccination
KW - Perinatally HIV infected children
KW - PIK3C2B
UR - http://www.scopus.com/inward/record.url?scp=85084561392&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85084561392&partnerID=8YFLogxK
U2 - 10.1016/j.clim.2020.108440
DO - 10.1016/j.clim.2020.108440
M3 - Article
C2 - 32330555
AN - SCOPUS:85084561392
VL - 215
JO - Clinical Immunology
JF - Clinical Immunology
SN - 1521-6616
M1 - 108440
ER -