Oral Vaccine Delivery: Can it Protect Against Non-mucosal Pathogens?

Lina Wang; Ross L Coppel


Expert Rev Vaccines. 2008;7(6):729-738. 

In This Article

Oral Vaccines

Vaccination is an efficient and cost-effective form of preventing infectious diseases. However, most currently available vaccines are delivered by injection, which makes mass immunization more costly and less safe, particularly in resource-poor developing countries. Oral vaccines have several attractive features compared with parenteral vaccines, but studies on their use have been limited almost exclusively to protection against mucosally transmitted pathogens. Their potential for controlling non-mucosally transmitted diseases has not yet been appreciated in general. In this article, we provide evidence that oral immunization is a feasible alternative for preventing infections transmitted through non-mucosal routes, including infections such as malaria, Japanese encephalitis and hepatitis B. Although there are still hurdles to overcome before such approaches can be deployed widely, recent progress in the oral vaccination field and the availability of a range of delivery systems offers hope for the development of a larger number of oral vaccines.

Prevention of infections by vaccination has proven to be an efficient and cost-effective strategy for public-health improvement. Most commercial vaccines available today are delivered by injection, with problems of safety, patient acceptability and morbidity. In recent years, there have been advances in methods of needle-free vaccine delivery, among which, oral delivery is of particular interest.[1,2,3] Oral delivery offers a number of significant advantages over other routes of administration.[4] Oral vaccines are cheaper to administer since they can be delivered outside of a formal clinical setting without the need for trained personnel. Elimination of needles from the vaccination process can negate concerns regarding the reuse and disposal of needles, which has been shown to be responsible for a number of vaccination-related infections.[5,6] Oral vaccines may also be cheaper to produce as a result of less stringent regulatory requirements for preparations that are administered per os compared with parenterally. However, oral vaccination has been regarded historically as likely to be less effective, as vaccine antigens undergo digestion in the GI tract prior to induction of an immune response. At present, there are a limited number of oral vaccines approved for human use, but many more are in the late stages of clinical development.[1,3]

Orally delivered vaccines are processed and presented by the digestive tract's immune system, often referred to as the gut-associated lymphoid tissue (GALT). The GALT is a complex system consisting of inductive sites (where antigens are encountered and responses are initiated) and effector sites (where local immune responses occur) linked by a homing system, whereby cells induced by antigen in the GALT migrate to the circulation and, subsequently, colonize the mucosa.[2] As a result, oral vaccination can induce immune responses locally in the gut and at distant mucosal sites, as well as systemic humoral and cellular immune responses. Oral vaccination typically generates a large amount of secretory IgA (sIgA), which plays a major role in mucosal defense. Accordingly, studies have focused on pathogens that enter the body through mucosal surfaces and cause diseases of the intestinal, respiratory and genital tracts.[1,2,3] There has been relatively less focus on the development of oral vaccines against pathogens that enter the body through routes other than the mucosa, such as blood, and that may manifest disease by colonization of non-mucosal tissues and organs. In this article, we summarize recent progress on oral vaccine delivery and explore the feasibility of such an approach to protect against diseases transmitted through non-mucosal routes. We focus on malaria, a disease caused by the protozoan parasite Plasmodium and transmitted by mosquitos. We also review work on several other diseases, including Japanese encephalitis (caused by a mosquito-borne virus) and hepatitis B (a viral disease transmitted principally through blood or serum transfer).


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