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  • Cristina Dragani MPharm

Why develop mucosal vaccines

Protective mucosal immune responses are most effectively induced by mucosal immunization via oral, nasal, intestinal, or vaginal routes, but most vaccines in use today are administered by injection.

Mucosal immune responses function as the first line of defense

Most infectious agents enter the body from mucosal surfaces, and therefore mucosal immune responses function as the first line of defense. The induction of mucosal immune responses occurs in the organized lymphoid tissues of the mucosa or draining lymph nodes. Mucosal immune responses are multiple and include both the antibody response, with mucosal IgG produced locally, and the cellular response by cytotoxic T lymphocytes, which are present in the mucosa. In addition, secretory IgA is also produced, which provides a first line of defense, preventing pathogen entry into the mucosa [Li et al. 2020].

Protective mucosal immune responses are most effectively induced by mucosal immunization via oral, nasal, intestinal, or vaginal routes, but most vaccines in use today are administered by injection. Among other things, injected vaccines are generally poor inducers of mucosal immunity and, for this reason, require relatively high dosages and adjuvant chemicals, which have often been investigated for side effects of vaccination [Hawkes et al., 2015]. The field of mucosal vaccine research has shown significant progress in recent years. However, in order to achieve optimal systems for mucosal vaccination, there are still many studies to be conducted, implying that the development and commercialization of mucosal vaccines require time and extensive scientific research.

Understanding how exposure to viruses and bacteria affects host immunity may have important implications for the development of mucosal vaccines, the purpose of which is to stimulate comprehensive, effective, and defensive immunity. Significant improvements in expression vectors, antigen selection and expression, as well as antigen stability and localization must be achieved before mucosal vaccines can be commercialized. In the coming years, clinical trials of new mucosal vaccines will be critical.

Success in mucosal vaccine research will depend largely on the continued research of scientists, their creativity and ingenuity, and will have great potential to promote human well-being.

Few or no adverse events expected with mucosal vaccine

The mucosal vaccine does not contain chemical adjuvant agents, but it is the probiotic lactic acid bacteria themselves, which are the carriers of the vaccine, that have an adjuvant, immune-boosting effect. These microorganisms represent the largest group of probiotic bacteria in the gut and are recognized as safe bacteria. They possess immunomodulatory actions and are effective as novel vaccine adjuvants. In addition, because mucosal probiotic vaccines are administered orally or nasally, they have higher acceptance and better safety, and also avoid the risk of contamination and/or possible accidents due to needles and syringes [Mojgani et al., 2020]. In particular, the ability of Lactobacillus to express viral antigens, and its ability to differentially modulate innate and adaptive immune responses in the intestinal and respiratory mucosa after its oral administration, indicates the potential of Lactobacillus in the development of a mucosal vaccine against Covid-19 [Villena et al., 2021]. Major side effects of the mucosal vaccine are not expected because the immune stimulation it performs resembles gentle immune stimulation. In addition, it is possible to take the mucosal vaccine in a series of doses that allow the immune response to gradually increase without causing any local and/or systemic inflammation. With the mucosal vaccine, there will therefore be no soreness, redness, or swelling of the injection site, as the mucosal vaccine will not be injected.


Hawkes D, Benhamu J, Sidwell T, Miles R, Dunlop RA.

Revisiting adverse reactions to vaccines: A critical appraisal of Autoimmune Syndrome Induced by Adjuvants (ASIA). J Autoimmun.

Li M, Wang Y, Sun Y, Cui H, Zhu SJ, Qiu HJ.

Mucosal vaccines: Strategies and challenges.

Immunol Lett. 2020;217:116-125. doi:10.1016/j.imlet.2019.10.013

Mojgani N, Shahali Y, Dadar M.

Immune modulatory capacity of probiotic lactic acid bacteria and applications in vaccine development. Benef Microbes. 2020;11(3):213-226.

Villena J, Li C, Vizoso-Pinto MG, Sacur J, Ren L, Kitazawa H.

Lactiplantibacillus plantarum as a Potential Adjuvant and Delivery System for the Development of SARS-CoV-2 Oral Vaccines. Microorganisms. 2021;9(4):683. Published 2021 Mar 26.

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