Abstract
Severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) infection, the causative agent of COVID-19, now represents the sixth Public Health Emergency of International Concern (PHEIC)—as declared by the World Health Organization (WHO) since 2009. Considering that SARS-CoV-2 is mainly transmitted via the mucosal route, a therapy administered by this same route may represent a desirable approach to fight SARS-CoV-2 infection. It is now widely accepted that genetically modified microorganisms, including probiotics, represent attractive vehicles for oral or nasal mucosal delivery of therapeutic molecules. Previous studies have shown that the mucosal administration of therapeutic molecules is able to induce an immune response mediated by specific serum IgG and mucosal IgA antibodies along with mucosal cell-mediated immune responses, which effectively concur to neutralize and eradicate infections. Therefore, advances in the modulation of mucosal immune responses, and in particular the use of probiotics as live delivery vectors, may encourage prospective studies to assess the effectiveness of genetically modified probiotics for SARS-CoV-2 infection. Emerging trends in the ever-progressing field of vaccine development re-emphasize the contribution of adjuvants, along with optimization of codon usage (when designing a synthetic gene), expression level, and inoculation dose to elicit specific and potent protective immune responses. In this review, we will highlight the existing pre-clinical and clinical information on the use of genetically modified microorganisms in control strategies against respiratory and non-respiratory viruses. In addition, we will discuss some controversial aspects of the use of genetically modified probiotics in modulating the cross-talk between mucosal delivery of therapeutics and immune system modulation.
Highlights
The end of 2019 was marked with the beginning of the COVID-19 outbreak caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [1]
Experience in the past decades have clearly demonstrated that a shift from traditional needle-based immunization to a needle-free one can overcome a number of limitations, accelerating large vaccination programs, in resource-limited developing countries
Studies within this area of investigation have led to discover that mucosal immunization, which entails the delivery of heterologous proteins to mucosal surfaces, is one of the few needle-free approaches that can exert significant prophylactic and therapeutic effects [106,107,108]
Summary
The end of 2019 was marked with the beginning of the COVID-19 outbreak caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [1]. Over the last two decades, research on the use of LAB as live vectors in the development of mucosal vaccines has focused on the construction of genetically modified (or recombinant), strains of the species: Lactobacillus plantarum, Lactobacillus casei, Lactobacillus acidophilus, Lactobacillus delbrueckii, and Lactococcus lactis able to produce numerous respiratory and non-respiratory virus-derived antigens (among others) (Table 1) Based on these pioneering studies, we can envisage that recombinant. Despite numerous reports on the use of recombinant LAB and their demonstrated potential in inducing mucosal immune responses and the prevention of respiratory viral infections, to our knowledge no studies to date have explored the use of recombinant probiotics in the development of vaccines to treat. Ongoing project; the final results will be made available on 28 February 2022
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