Steinhoff, MC; Katz, J; Englund, JA; Khatry, SK; Shrestha, L; Kuypers, J; Stewart, L; Mullany, L; Chu, HY; LeClerq, SC; Kozuki, N; McNeal, M; Reedy, AM; Tielsch, JM. Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial .Lancet Infectious Diseases. 2017; 17(9):981-989.
This paper addresses the impact of maternal influenza immunization in a part of the world where influenza viruses circulate year-round. This was a randomized, placebo-controlled trial enrolling more than 3600 women. Conducting influenza immunizations year-round significantly reduced maternal influenza-like illness and influenza in infants. The most striking impact observed, perhaps unexpected, was a major effect on prevention of low birthweight. The study is an important one because it extends the benefits of maternal immunization to the prevention of low birthweight, and provides warranted evidence for the need for year-round maternal immunization in subtropical regions of the world.
Liu, Y; Xu, S; Woodruff, AL; Xia, M; Tan, M; Kennedy, MA; Jiang, X. Structural basis of glycan specificity of P[19] VP8*: Implications for rotavirus zoonosis and evolution. PLoS pathogens. 2017; 13(11).
Rotaviruses (RVs) are diverse in host specificity, infecting humans and/or animals, but the molecular mechanism behind such diverse host specificity remained elusive. In this study, we resolved the crystal structures of the host receptor-binding domain (VP8*) of an important RV (P[19] genotype) in complex with its glycan receptors and elucidated the structural basis of how RVs switch their host specificity via changing their receptor binding site to adapt their new host receptors. Through genetic analyses we also found related sequence changes in other RV genotypes and genogroups, leading to an important hypothesis of RV divergent evolution under selection of their host glycan receptor makeups. These advancements explain current RV diversity, in which some RVs exclusively infect humans or animals but others infect both, significantly improved our understanding of RV disease burden, epidemiology and vaccine development against RVs.
Biggs, HM; McNeal, M; Nix, WA; Kercsmar, C; Curns, AT; Connelly, B; Rice, M; Chern, SW; Prill, MM; Back, N; Oberste, MS; Gerber, SI; Staat, MA. Enterovirus D68 Infection Among Children With Medically Attended Acute Respiratory Illness, Cincinnati, Ohio, July-October 2014. Clinical Infectious Diseases. 2017; 65(2):315-323.
Coincident with the timing of the US EV-D68 epidemic, Cincinnati Children’s Hospital Medical Center conducted prospective, population-based surveillance for acute respiratory illness (ARI) among children <13 years of age in the emergency department (ED) and inpatient hospital settings. The detection found of EV-D68 was 25% of ARI hospitalizations and 11% of ARI ED visits with rates of 1.3 (95% confidence interval [CI], 1.0-1.6) and 8.4 per 1000 children <13 years of age, respectively. Preexisting asthma associates with EV-D68 infection (adjusted odds ratio, 3.2; 95% CI, 2.0-5.1). Compared with other ARI, children with EV-D68 were more likely admitted to a hospital from the ED (P ≤ .001), receive supplemental oxygen (P = .001), and require intensive care unit admission (P = .04). During the 2014 EV-D68 epidemic, we found high rates of pediatric hospitalizations and ED visits associated with EV-D68 and children with asthma were at increased risk for medically attended EV-D68 illness. Having an established ARI surveillance program in place, allowed us to provide the only prospective, population-based, PCR confirmed EV-D68 rates in the US for this epidemic.
Lange, SM; McKell, MC; Schmidt, SM; Hossfeld, AP; Chaturvedi, V; Kinder, JM; McAlees, JW; Lewkowich, IP; Way, SS; Turner, J; Qualls, JE. L-citrulline Metabolism in Mice augments cD4(+) T cell Proliferation and cytokine Production In Vitro, and accumulation in the Mycobacteria-infected lung. Frontiers in Immunology. 2017; 8(NOV).
Activation, recruitment, and effector function of T lymphocytes are essential for host defenses and pathogen control. In addition to classical signals, including ligation of the T cell and co-stimulatory receptors (signals 1 and 2) and cytokine stimulation (signal 3), nutrient acquisition is an underappreciated “signal 4” required for T lymphocyte function. L-arginine has long known as an immune-modulating nutrient, and limiting this amino acid in vitro or in vivo restricts T lymphocyte immune responses. Interestingly, providing a related amino acid – L-citrulline – rescues T lymphocyte proliferation and cytokine production even in the absence of L-arginine. In the present work, we demonstrated that L-arginine synthesis from the requirement of L-citrulline for T lymphocyte function, and eliminating this pathway significantly reduced accumulation of pathogen-specific T lymphocytes to mycobacteria-infected tissues. We anticipate further research on this and other “immunonutrient” utilization pathways will yield novel approaches in regulating immune function.
Widdice, LE; Unger, ER; Panicker, G; Hoagland, R; Callahan, ST; Jackson, LA; Berry, AA; Kotloff, K; Frey, SE; Harrison, CJ; Pahud, BA; Edwards, KM; Mulligan, MJ; Sudman, J; Bernstein, DI. Antibody responses among adolescent females receiving two or three quadrivalent human papillomavirus vaccine doses at standard and prolonged intervals. Vaccine. 2018; 36(6):881-889.
Until recently, the recommendation is for a three dose schedule (0, 2, 6 months) for all adolescents receiving HPV vaccination. Currently, the recommendation is for a two dose schedule (0, 6) for adolescents initiating vaccination before age 15. A majority of girls receive doses at longer intervals that recommended. The findings of this study suggest that delays in administration of either of the HPV vaccine doses, beyond twice as long as the recommended intervals, will not negatively affect the protection offered by HPV vaccination. The results of this trial also support recent recommendations of the two-dose regimen in 9–14 year olds and that antibody responses after two doses at prolonged intervals were similar among 9-14 and 15-17 year olds.