Immunogenicity of pneumococcal conjugate vaccine formulations containing pneumococcal proteins, and immunogenicity and reactogenicity of co-administered routine vaccines - A phase II, randomised, observer-blind study in Gambian infants
VACCINE
Authors: Odutola, Aderonke; Ota, Martin O. C.; Antonio, Martin; Ogundare, Ezra O.; Saidu, Yauba; Owiafe, Patrick K.; Worwui, Archibald; Idoko, Olubukola T.; Owolabi, Olumuyiwa; Kampmann, Beate; Greenwood, Brian M.; Alderson, Mark; Traskine, Magali; Swinnen, Kristien; Verlant, Vincent; Dobbelaere, Kurt; Borys, Dorota
Abstract
Background: Two conserved pneumococcal proteins, pneumolysin toxoid (dPly) and pneumococcal histidine triad protein D (PhtD), combined with 10 polysaccharide conjugates from the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) in two investigational pneumococcal vaccine (PHiD-CV/dPly/PhtD) formulations were immunogenic and well-tolerated when administered to Gambian children. Here, we report immunogenicity of the polysaccharide conjugates, and immunogenicity and reactogenicity of co-administered routine vaccines. Methods: In this phase II, controlled, observer-blind, single-centre study, healthy infants aged 810 weeks were randomised (1:1:1:1:1:1) to six groups. Four groups received 3+0 schedule (2-3-4 months [M]) of PHiD-CV/dPly/PhtD (10 or 3014 of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine; and two groups received 2+1 schedule (2-4-9 M) of PHiD-CV/dPly/PhtD (30 mu g of each protein) or PHiD-CV. All infants received diphtheria-tetanus-whole cell pertussis-hepatitis B-Haemophilus influenzae type b (DTPw-HBV/Hib) and oral trivalent polio vaccines (OPV) at 2-3-4 M, and measles, yellow fever, and OPV vaccines at 9 M. We evaluated immune responses at 2-5-9-12 M; and reactogenicity 0-3 days post-vaccination. Results: 1200 infants were enrolled between June 2011 and May 2012; 1152 completed the study. 1 M post-primary vaccination, for each PHiD-CV serotype except 6B and 23F, >= 97.4% (3+0 schedule) and >= 96.4% (2+1 schedule) of infants had antibody concentrations >= 0.2 mu g/mL. Immune responses were comparable between groups within the same vaccination schedules. Observed antibody geometric mean concentrations (GMCs) increased by 1 M post-primary vaccination compared to pre-vaccination. In the following months, GMCs and opsonophagocytic activity titres waned, with an increase post-booster for the 2+1 schedule. Immune responses to protein D and, DTPw-HBV/Hib, OPV, measles, and yellow fever vaccines were not altered by co-administration with pneumococcal proteins. Reactogenicity of co-administered vaccines was comparable between groups and did not raise concerns. Conclusion: Immune responses to the 10 PHiD-CV polysaccharide conjugates-administered vaccines were not altered by addition of dPly and PhtD. (C) 2019 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.
Pregnancy favors circulating IL-21-secreting T-FH-like cell recovery in ARV-treated HIV-1-infected women
AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY
Authors: Kasahara, Taissa M.; Monteiro, Clarice; Hygino, Joana; Cafasso, Marcos O. S. D.; Oyamada, Hugo A. A.; Andrade, Regis M.; Ferreira, Orlando; Leite, Simone; Silva, Vander G.; Gupta, Sudhir; Bento, Cleonice A. M.
Abstract
Problem Pregnancy appears to favor maternal antibody production. In contrast, by damaging follicular helper T cells (T-FH), HIV-1 infection compromises protective humoural immune response. Therefore, we aimed to investigate the frequency of different T-FH-like cells in HIV-infected pregnant women (PW) before and after antiretroviral (ARV) therapy. Method of study Peripheral blood mononuclear cells, CD4(+) T and B cells, were obtained from asymptomatic HIV-1-infected non-PW and PW just before and after ARV therapy. In some experiments, healthy HIV-1-negative PW were also tested. The frequency of different T-FH-like cell subsets was determined by flow cytometry. The plasma titers of IgG anti-tetanus toxoid (TT), anti-HBsAg, and anti-gp41 were determined by ELISA. The in vitro production of total IgG, IL-21, and hormones (estrogen and progesterone) was quantified also by ELISA. Results Our results demonstrate that antiretroviral (ARV) therapy was more efficient in elevating the percentage of circulating IL-21-secreting T-FH cells in HIV-1-infected pregnant women (PW) than in non-pregnant patients (nPW). Moreover, in co-culture systems, CD4(+) T cells from ART-treated PW were more efficient in assisting B cells to produce IgG production. The in vivo anti-HBsAg IgG titers after ARV therapy were also significantly higher in PW, and their levels were directly associated with both IL-21(+)T(FH) frequency and plasma concentration of estrogen. Conclusion In summary, our results suggest that pregnancy favors the recovery of T-FH-like cells after ARV therapy in HIV-1-infected women, which could help these mothers to protect their newborns from infectious diseases by transferring IgG across the placenta.