Clin Exp Vaccine Res.  2021 Sep;10(3):229-239. 10.7774/cevr.2021.10.3.229.

Staphylococcus aureus derived hyaluronic acid and bacillus Calmette-Guérin purified proteins as immune enhancers to rabies vaccine and related immuno-histopathological alterations

• Shebl RI
• Amer ME
• Abuamara TMM
• Matar ER
• Ahmed HF
• Gomah TA
• El Moselhy LE
• Abu-Elghait M
• Mohamed AF

• KMID: 2525819
• DOI: http://doi.org/10.7774/cevr.2021.10.3.229

Abstract

Purpose
One of the essential goals regarding the successful control of rabies infection is the development of a safe, effective, and inexpensive vaccine. the current study aimed to evaluate the inactivation potential of β-propiolactone (βPL), binary ethyleneimine (BEI), and hydrogen peroxide (H₂O₂).
Materials and Methods
Estimating the inactivation kinetics of βPL, BEI, and H₂O₂ revealed that the tested inactivants could completely and irreversibly inactivate rabies virus within 2, 12, and 4 hours, respectively while maintaining its viral immunogenicity. The potency of βPL, BEI, and H₂O₂ inactivated vaccines was higher than the World Health Organization acceptance limit and were in the order of 3.75, 4.21, and 3.64 IU/mL, respectively. Monitoring the humoral and cellular immunity elicited post-immunization using Staphylococcus aureus derived hyaluronic acid (HA) and bacillus Calmette-Guérin purified protein derivative (PPD) adjuvanted rabies vaccine candidates were carried out using enzyme-linked immunosorbent assay.
Results

Results
demonstrated that both adjuvants could progressively enhance the release of anti-rabies total immunoglobulin G as well as the pro-inflammatory mediators (interferon-gamma and interleukin-5) relative to time. However, a higher immune response was developed in the case of HA adjuvanted rabies vaccine compared to PPD adjuvanted one. The harmful consequences of the tested adjuvants were considered via investigating the histopathological changes in the tissues of the immunized rats using hematoxylin and eosin stain. Lower adverse effects were observed post-vaccination with HA and PPD adjuvanted vaccines compared to that detected following administration of the currently used alum as standard adjuvant.
Conclusion
Our findings suggested that HA and PPD could serve as a promising platform for the development of newly adjuvanted rabies vaccines with elevated immune enhancing potentials and lower risk of health hazards.

Keyword

β-Propiolactone; Binary ethyleneimine; Immune enhancers; Hyaluronic acid; Rabies vaccines