Subunit nanovaccine elicited T cell functional activation controls Trypanosoma cruzi mediated maternal and placental tissue damage and improves pregnancy outcomes in mice

• Published in: npj vaccines Vol. 8; no. 1; p. 188
• Main Authors: Rios, Lizette Elaine, Lokugamage, Nandadeva, Choudhuri, Subhadip, Chowdhury, Imran Hussain, Garg, Nisha Jain
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16-12-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250/255; 631/250/590; 692/420/254; Biomedical and Life Sciences; Biomedicine; Females; Fertility; Histology; Immune response; Immunization; Infections; Infectious Diseases; Medical Microbiology; Parasites; Placenta; Pregnancy; Public Health; Rodents; Tissues; Vaccine; Vaccines; Virology
• ISSN: 2059-0105; 2059-0105
• DOI: 10.1038/s41541-023-00782-z

This study investigated a candidate vaccine effect against maternal
Trypanosoma cruzi (Tc)
infection and improved pregnancy outcomes. For this,
TcG2
and
TcG
4 were cloned in a nanoplasmid optimized for delivery, antigen expression, and regulatory compliance (nano2/4 vaccine). Female C57BL/6 mice were immunized with nano2/4, infected (
Tc
SylvioX10), and mated 7-days post-infection to enable fetal development during the maternal acute parasitemia phase. Females were euthanized at E12–E17 (gestation) days. Splenic and placental T-cell responses were monitored by flow cytometry. Maternal and placental/fetal tissues were examined for parasites by qPCR and inflammatory infiltrate by histology. Controls included age/immunization-matched non-pregnant females. Nano2/4 exhibited no toxicity and elicited protective IgG2a/IgG1 response in mice. Nano2/4 signaled a splenic expansion of functionally active CD4+ effector/effector memory (Tem) and central memory (Tcm) cells in pregnant mice. Upon challenge infection, nano2/4 increased the splenic CD4+ and CD8+T cells in all mice and increased the proliferation of CD4+Tem, CD4+Tcm, and CD8+Tcm subsets producing IFNγ and cytolytic molecules (PRF1, GZB) in pregnant mice. A balanced serum cytokines/chemokines response and placental immune characteristics indicated that pregnancy prevented the overwhelming damaging immune response in mice. Importantly, pregnancy itself resulted in a significant reduction of parasites in maternal and fetal tissues. Nano2/4 was effective in arresting the
Tc
-induced tissue inflammatory infiltrate, necrosis, and fibrosis in maternal and placental tissues and improving maternal fertility, placental efficiency, and fetal survival. In conclusion, we show that maternal nano2/4 vaccination is beneficial in controlling the adverse effects of
Tc
infection on maternal health, fetal survival, and pregnancy outcomes.