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Novel Tuberculosis (TB) Oral Vaccine Candidate: Enhancing Mucosal Immunity with Recombinant Secretory IgA (SIgA) in Goat Milk
* 1 , 1 , 2, 3 , 1 , 1, 4 , * 1
1  School of Health Sciences, Universiti Sains Malaysia, Health Campus, Kubang Kerian, 16150, Kelantan Darul Naim, Malaysia
2  Recombinant Biopharmaceuticals Laboratory, Pharmacology Department, School of Biological Sciences, Universidad de Concepcion, Concepcion, Chile
3  Center for Biotechnology and Biomedicine Spa, Concepcion, Chile
4  Malaysia Genome and Vaccine Institute, National Institutes of Biotechnology Malaysia, 43000 Kajang, Selangor Darul Ehsan, Malaysia
Academic Editor: Yee-Joo Tan

Abstract:

The Bacillus Calmette–Guérin (BCG) vaccine, the only licensed tuberculosis (TB) vaccine, has limited effectiveness in preventing pulmonary TB in adults. Our study explores using the mammary gland of non-transgenic goats to produce an oral vaccine candidate, combining secretory IgA (SIgA) with epitopes from TB. This approach aims to enhance mucosal immunity and provide comprehensive protection across different stages of TB infection. The vaccine candidate was developed by engineering recombinant epitopes including Antigen 85b (Ag85b) for active TB, alpha-crystallin (Acr) for latent TB, and resuscitation-promoting factor E (RpfE) for reactivated TB combined with SIgA. We evaluated the immunological response by administering goat milk containing the recombinant protein directly as oral immunization. Five groups of Balb/C mice (n=5) were categorized as follows: recombinant milk (RM), normal milk (NM), BCG prime with RM boost (BCG-RM), BCG prime with NM boost (BCG-NM), and BCG alone (BCG). The RM and NM groups received daily oral immunizations with RM or NM for two weeks. The BCG-primed groups received booster doses of RM or NM daily for two weeks, one month after the initial BCG vaccination. Two weeks after the final immunization, the mice were sacrificed, and IgA levels in the saliva and lung lavage were measured using enzyme-linked immunosorbent assay (ELISA). Mice immunized with recombinant vaccine-containing milk, especially those primed with BCG, showed a significant increase in IgA levels in the saliva and lung lavage compared to the normal milk and BCG-only groups. These results indicate that the recombinant vaccine-containing milk can effectively induce a strong mucosal immune response against TB. The significant increase in IgA levels in mice, particularly in BCG-primed groups, highlights the potential of this vaccine as a booster candidate with BCG priming.

Keywords: Mucosal; Mammary-gland; Milk vaccine
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