Frenck, RW Jr; Ervin, J; Chu, L; Abbanat, D; Spiessens, B; Go, O; Haazen, W; van den Dobbelsteen, G; Poolman, J; Thoelen, S; de Palacios, PI. Safety and immunogenicity of a vaccine for extra-intestinal pathogenic Escherichia coli ESTELLA a phase 2 randomised controlled trial. Lancet Infectious Diseases. 2019; 19(6):631-640.
Extra-intestinal pathogenic Escherichia coli (ExPEC) causes most urinary tract infections, is the second most common cause of neonatal bacteraemia and meningitis, and is a leading cause of adult invasive ExPEC disease, particularly bacteraemia and sepsis. The risk of developing ExPEC bacteremia and sepsis increases with age. This Phase 1 study demonstrated that a parenteral multivalent E coli O-antigen bioconjugate vaccine was well tolerated and elicited robust and functional antibody responses. Advancement of the vaccine into further clinical trials is planned.
Xia, M; Huang, P; Sun, C; Han, L; Vago, FS; Li, K; Zhong, W; Jiang, W; Klassen, JS; Jiang, X; Tan, M. Bioengineered Norovirus S-60 Nanoparticles as a Multifunctional Vaccine Platform. ACS Nano. 2018; 12(11):10665-10682.
This paper describes a technology to produce 60-valent shell (S) nanoparticles through bioengineering of norovirus S domains that naturally constitute the interior shell of norovirus capsid. The S60 nanoparticles may serve as a potent nanoplatform to display foreign antigens for improved immunogenicity for novel vaccine development. As a proof concept, a chimeric S60 nanoparticle displaying rotavirus neutralizing antigen VP8*, referred as S60-VP8* nanoparticle, has been developed and characterized. Our data demonstrated that this S60-VP8* nanoparticle vaccine elicited high antibody response in mice, the vaccine-immunized mouse sera neutralized rotavirus replication, and the vaccine protected immunized mice from rotavirus infection. Thus, the norovirus S60 nanoparticle is a multifunctional nanoplatform to display various antigens for novel vaccine development against different infectious diseases.
Tan, M; Cui, L; Huo, X; Xia, M; Shi, F; Zeng, X; Huang, P; Zhong, W; Li, W; Xu, K; Chen, L; Zhou, M; Jiang, X. Saliva as a source of reagent to study human susceptibility to avian influenza H7N9 virus infection. Emerging Microbes and Infections. 2018; 7(1).
Avian influenza viruses, such as H7N9 that occasionally caused major epidemics in humans with high mortality rates are an important public health concern, but how these viruses jump to humans causing sporadic cases remains unknown. In this study, using a unique saliva binding assay we found that glycan receptors of H7N9 virus may be shared by a small sub-set of human population, explaining why only sporadic cases were seen during human H7N9 epidemics. The likelihood that majority human populations are naturally resistant to H7N9 viruses also suggests that these avian H7N9 viruses may not be able to survive in humans during the off-season, explaining their seasonal peaks matched with those of migration birds. These findings significantly advance our understanding of H7N9 epidemiology and help develop new strategies to control and prevent H7N9 caused epidemics. Saliva may be a useful reagent to study human susceptibility to influenza viruses in general.
Robinette, ED; Brower, L; Schaffzin, JK; Whitlock, P; Shah, SS; Connelly, B; AHO Care Algorithm Team. Use of a Clinical Care Algorithm to Improve Care for Children With Hematogenous Osteomyelitis. Pediatrics. 2019; 143(1).
Treatment regimens for acute hematogenous osteomyelitis (AHO)can be difficult to study due to infrequent occurrence and infrequent poor outcomes. This QI project successfully combined generation of a robust local consensus guideline, statistical process control measurement, and n-of-one testing to safely decrease the cost of care for pediatric AHO. It demonstrated that cost savings and improved clinical care are not mutually exclusive aims when change is undertaken in a systematic fashion with measurement in place.
Spearman, P; Tomaras, GD; Montefiori, DC; Huang, Y; Elizaga, ML; Ferrari, G; Munir Alam, S; Isaacs, A; Ahmed, H; Hural, J; Juliana McElrath, M; Ouedraogo, L; Pensiero, M; Butler, C; Kalams, SA; Overton, ET; Barnett, SW; HVTN 088 Protocol Team and the NIH/NIAID HIV Vaccine Trials Network. Rapid boosting of HIV-1 neutralizing antibody responses in humans following a prolonged immunologic rest period. Journal of Infectious Diseases. 2019; 219(11):1755-1765.
HIV vaccines have failed to generate broadly neutralizing antibodies that are needed for protection. This paper describes a clinical trial in which subjects received a heterologous protein boost many years after receiving “priming” with an envelope protein vaccine from another clade. While neutralization breadth was not improved, the results showed a very robust and rapid boosting of cellular and humoral responses, demonstrating long-term memory responses. This is the first report showing such durable memory responses from HIV vaccines in humans, and demonstrating that a single protein boost can elicit robust recall responses.