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Neutralizing activity induced by the attenuated coxsackievirus B3 Sabin3-like strain against CVB3 infection
Nadia Jrad-Battikh1, Amira Souii, Leila Oueslati
1Laboratoire des Maladies Transmissibles et Substances Biologiquement Actives (LR99-ES27), Faculté de Pharmacie de Monastir, Avenue Avicenne, 5000, Biotola, Tunisia.
Insights
A Sabin3-like mutant of Coxsackievirus B3 (CVB3) shows promise as an attenuated vaccine candidate. It induced protective immunity against CVB3 and CVB4 E2 in mice, preventing myocarditis and pancreatitis.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Coxsackievirus B3 (CVB3) is a significant cause of viral myocarditis and dilated cardiomyopathy.
- Currently, no effective vaccine is available for clinical use against CVB3 infections.
Purpose of the Study:
- To evaluate the potential of a Sabin3-like mutant of CVB3 as an attenuated vaccine.
- To assess its ability to induce protective immunity against virulent CVB3 and CVB4 E2 strains in a mouse model.
Main Methods:
- Mice were inoculated with the Sabin3-like CVB3 mutant via oral or intraperitoneal (IP) routes.
- Serum samples were analyzed for anti-CVB3 neutralizing activity.
- Mice were subsequently challenged with virulent CVB3 Nancy or CVB4 E2 strains.
- Viral titers, antibody responses, myocarditis, and pancreatitis were assessed.
Main Results:
- The Sabin3-like CVB3 mutant was highly attenuated in vivo and induced anti-CVB3 serum activity.
- Immunized mice showed increased CVB3 neutralizing antibodies post-challenge compared to non-immunized controls.
- While protection was observed against CVB3 and CVB4 E2 challenge, neutralizing activity was specific to CVB3, not CVB4.
- Oral inoculation prevented pancreatic inflammation, unlike IP inoculation.
- All immunized mice were protected from myocarditis and pancreatitis.
Conclusions:
- The Sabin3-like CVB3 mutant demonstrates potential as an attenuated vaccine candidate.
- It effectively induces protective immunity against CVB3 and related strains, preventing associated pathologies.
- Oral administration appears safer, avoiding pancreatic inflammation observed with IP routes.
Abstract:
Coxsackievirus B3 (CVB3) causes viral myocarditis, and can ultimately result in dilated cardiomyopathy. There is no vaccine available for clinical use. In the present work, we assessed whether the Sabin3-like mutant of CVB3 could induce a protective immunity against virulent CVB3 Nancy and CVB4 E2 strains in mice by both oral and intraperitoneal (IP) routes. Serum samples, taken from mice inoculated with Sabin3-like, were assayed in vitro for their anti-CVB3 neutralizing activity. CVB3 Sabin3-like was highly attenuated in vivo and was able to induce an anti-CVB3 activity of the serum. However, at 4 days post-CVB3 challenge, significant increased titers of CVB3 neutralizing antibodies were detectable in the sera of immunized mice over the next 6 days. Non-immunized mice challenged with CVB3 Nancy had no anti-CVB3 activity in their sera until 10 days post-infection. CVB3 Nancy induced higher viral titers than did the mutant strain. There was no variation of the neutralizing activity of serum taken from mice immunized with CVB3 Sabin3-like and challenged with CVB4 E2, compared to non-immunized mice. Despite the fact that CVB3 and CVB4 are closely related viruses, virus-neutralizing activity clearly distinguish between these viruses. A variable and limited amount of pancreatic inflammation was seen in some mice 10 days after Sabin3-like inoculation by IP route, whereas there was no evidence of pancreatic damage in mice inoculated by oral route. All immunized mice were protected from myocarditis and pancreatitis at 8 days post-challenge with CVB3 or CVB4 E2. These findings strongly suggest that the mutant strain could be considered a candidate for an attenuated CVB3 vaccine.
