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.
The antibody response to the glycan alpha-Gal correlates with COVID-19 disease symptoms
JOURNAL OF MEDICAL VIROLOGY
Authors: Miguel Urra, Jose; Ferreras-Colino, Elisa; Contreras, Marinela; Cabrera, Carmen M.; Fernandez de Mera, Isabel G.; Villar, Margarita; Cabezas-Cruz, Alejandro; Gortazar, Christian; de la Fuente, Jose
Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide. Characterization of the immunological mechanisms involved in disease symptomatology and protective response is important to progress in disease control and prevention. Humans evolved by losing the capacity to synthesize the glycan Gal alpha 1-3Gal beta 1-(3)4GlcNAc-R (alpha-Gal), which resulted in the development of a protective response against pathogenic viruses and other microorganisms containing this modification on membrane proteins mediated by anti-alpha-Gal immunoglobulin M (IgM)/IgG antibodies produced in response to bacterial microbiota. In addition to anti-alpha-Gal antibody-mediated pathogen opsonization, this glycan induces various immune mechanisms that have shown protection in animal models against infectious diseases without inflammatory responses. In this study, we hypothesized that the immune response to alpha-Gal may contribute to the control of COVID-19. To address this hypothesis, we characterized the antibody response to alpha-Gal in patients at different stages of COVID-19 and in comparison with healthy control individuals. The results showed that while the inflammatory response and the anti-SARS-CoV-2 (Spike) IgG antibody titers increased, reduction in anti-alpha-Gal IgE, IgM, and IgG antibody titers and alteration of anti-alpha-Gal antibody isotype composition correlated with COVID-19 severity. The results suggested that the inhibition of the alpha-Gal-induced immune response may translate into more aggressive viremia and severe disease inflammatory symptoms. These results support the proposal of developing interventions such as probiotics based on commensal bacteria with alpha-Gal epitopes to modify the microbiota and increase alpha-Gal-induced protective immune response and reduce severity of COVID-19.