Mucosal vaccination: onward and upward

MV140 is an inactivated whole-cell bacterial mucosal vaccine with proven clinical efficacy against recurrent urinary tract infections (UTIs). These infections are primarily caused by uropathogenic E. coli (UPEC) strains, which are unique in their virulence factors and remarkably diverse. MV140 contains a non-UPEC strain, suggesting that it may induce an immune response against different UPEC-induced UTIs in patients. To verify this, we experimentally evaluated the cellular and humoral responses to UTI89, a prototypical UPEC strain, in mice vaccinated with MV140, as well as the degree of protection achieved in a UPEC UTI89 model of acute cystitis. The results show that both cellular (Th1/Th17) and antibody (IgG/IgA) responses to UTI89 were induced in MV140-immunized mice. MV140 vaccination resulted in an early increased clearance of UTI89 viable bacteria in the bladder and urine following transurethral infection. This was accompanied by a highly significant increase in CD4+ T cells in the bladder and an increase in urinary neutrophils. Collectively, our results support that MV140 induces cross-reactive humoral and cellular immune responses and cross-protection against UPEC strains.

Section: Discussionmentioning

confidence: 99%

MV140 Mucosal Vaccine Induces Targeted Immune Response for Enhanced Clearance of Uropathogenic E. coli in Experimental Urinary Tract Infection

Saz-Leal,

Ligon,

Diez-Rivero

et al. 2024

“…Some, but not all, adjuvants in parenteral vaccines have promoted mucosal immunity; the mechanism behind this is not yet understood [ 35 ]. Nevertheless, most workers in the field consider that an optimal mucosal immune response will result following mucosal exposure to the immunogen [ 36 , 37 , 38 , 39 , 40 ].…”

Section: History Of Vaccine Developmentmentioning

confidence: 99%

“…Most vaccines produce a systemic immune response, and while some animal studies have suggested that injected vaccines produce good mucosal immune responses, many parenterally administered vaccines that produce excellent humoral immune responses yield substantially worse mucosal immune responses [ 35 , 42 ]. Several studies have shown administering vaccines at a mucosal surface elicits the most effective mucosal immune responses [ 36 , 37 , 38 , 39 , 40 ].…”

Section: Importance Of Mucosal Vaccines and Their Developmentmentioning

confidence: 99%

Vaccine Strategies to Elicit Mucosal Immunity

Song,

Mehl,

Zeichner

2024

Vaccines are essential tools to prevent infection and control transmission of infectious diseases that threaten public health. Most infectious agents enter their hosts across mucosal surfaces, which make up key first lines of host defense against pathogens. Mucosal immune responses play critical roles in host immune defense to provide durable and better recall responses. Substantial attention has been focused on developing effective mucosal vaccines to elicit robust localized and systemic immune responses by administration via mucosal routes. Mucosal vaccines that elicit effective immune responses yield protection superior to parenterally delivered vaccines. Beyond their valuable immunogenicity, mucosal vaccines can be less expensive and easier to administer without a need for injection materials and more highly trained personnel. However, developing effective mucosal vaccines faces many challenges, and much effort has been directed at their development. In this article, we review the history of mucosal vaccine development and present an overview of mucosal compartment biology and the roles that mucosal immunity plays in defending against infection, knowledge that has helped inform mucosal vaccine development. We explore new progress in mucosal vaccine design and optimization and novel approaches created to improve the efficacy and safety of mucosal vaccines.

“…Mucosa-associated lymphoid cells share essential traits that include an epithelium-adapted profile, innate-like properties, cytotoxic potential, the ability to initiate immune responses to novel antigens, and the ability to produce cellular effectors of immune protection together with antibodies of the IgA class [ 13 ]. Though the different mucosal systems are interacting, it should be noted that some compartmentalization needs to be considered since nasal immunization mostly protects the respiratory tract and—while it is known that oral immunization is effective for salivary glands and parts of the intestine and mammary glands—is almost ineffective for the genital tract [ 14 ]. Thus, generalizations must be avoided.…”

Section: The Mucosal Immune Systemmentioning

confidence: 99%

mRNA Technology and Mucosal Immunization

Toniolo,

Maccari,

Camussi

2024

Current mRNA vaccines are mainly administered via intramuscular injection, which induces good systemic immunity but limited mucosal immunity. Achieving mucosal immunity through mRNA vaccination could diminish pathogen replication at the entry site and reduce interhuman transmission. However, delivering mRNA vaccines to mucosae faces challenges like mRNA degradation, poor entry into cells, and reactogenicity. Encapsulating mRNA in extracellular vesicles may protect the mRNA and reduce reactogenicity, making mucosal mRNA vaccines possible. Plant-derived extracellular vesicles from edible fruits have been investigated as mRNA carriers. Studies in animals show that mRNA vehiculated in orange-derived extracellular vesicles can elicit both systemic and mucosal immune responses when administered by the oral, nasal, or intramuscular routes. Once lyophilized, these products show remarkable stability. The optimization of mRNA to improve translation efficiency, immunogenicity, reactogenicity, and stability can be obtained through adjustments of the 5′cap region, poly-A tail, codons selection, and the use of nucleoside analogues. Recent studies have also proposed self-amplifying RNA vaccines containing an RNA polymerase as well as circular mRNA constructs. Data from parenterally primed animals demonstrate the efficacy of nasal immunization with non-adjuvanted protein, and studies in humans indicate that the combination of a parenteral vaccine with the natural exposure of mucosae to the same antigen provides protection and reduces transmission. Hence, mucosal mRNA vaccination would be beneficial at least in organisms pre-treated with parenteral vaccines. This practice could have wide applications for the treatment of infectious diseases.