Protection against herpes simplex virus type 2 infection in a neonatal murine model using a trivalent nucleoside-modified mRNA in lipid nanoparticle vaccine
VACCINE
Authors: LaTourette, Philip C., II; Awasthi, Sita; Desmond, Angela; Pardi, Norbert; Cohen, Gary H.; Weissman, Drew; Friedman, Harvey M.
Abstract
Neonatal herpes is a dreaded complication of genital herpes infection in pregnancy. We recently compared two vaccine platforms for preventing genital herpes in female mice and guinea pigs and determined that HSV-2 glycoproteins C, D and E expressed using nucleoside-modified mRNA in lipid nanoparticles provided better protection than the same antigens produced as baculovirus proteins and administered with CpG and alum. Here we evaluated mRNA and protein immunization for protection against neonatal herpes. Female mice were immunized prior to mating and newborns were infected intranasally with HSV-2. IgG binding and neutralizing antibody levels in mothers and newborns were comparable using the mRNA or protein vaccines. Both vaccines protected first and second litter newborns against disseminated infection based on virus titers in multiple organs. We conclude that both vaccines are efficacious at preventing neonatal herpes, which leaves the mRNA vaccine as our preferred candidate based on better protection against genital herpes. (C) 2020 Elsevier Ltd. All rights reserved.
Evaluation of CpG-ODN-Adjuvanted Toxoplasma gondii Virus-Like Particle Vaccine upon One, Two, and Three Immunizations
PHARMACEUTICS
Authors: Kang, Hae-Ji; Chu, Ki-Back; Kim, Min-Ju; Park, Hyunwoo; Jin, Hui; Lee, Su-Hwa; Moon, Eun-Kyung; Quan, Fu-Shi
Abstract
Successful vaccines against specific pathogens often require multiple immunizations and adjuvant usage. Yet, assessing the protective efficacy of different immunization regimens with adjuvanted Toxoplasma gondii vaccines remains elusive. In this study, we investigated the vaccine efficacy induced by CpG-ODN-adjuvanted T. gondii virus-like particles (VLPs) after challenge infection with T. gondii (ME49) in mice (BALB/c) upon one, two, and three immunizations. Immunization with adjuvanted T. gondii VLPs induced higher levels of T. gondii-specific IgG and/or IgA antibody responses, germinal center (GC) B cells, total B cells, and CD4(+) and CD8(+) T cells compared with unadjuvanted VLPs. Increasing the number of immunizations was strongly correlated with enhanced protective immunity against T. gondii in mice, with the highest protection being demonstrated in mice thrice-immunized with either adjuvanted T. gondii VLPs or VLPs alone. Notably, lesser bodyweight reductions and cerebral cyst counts were observed in mice receiving multiple immunizations with the adjuvanted VLPs, thereby confirming the effectiveness of adjuvanted boost immunizations. These results demonstrated that multiple immunizations with T. gondii VLPs is an effective approach, and the CpG-ODN can be developed as an effective adjuvant for T. gondii VLP vaccines.