The role of adjuvants in the development of mucosal vaccines

Abstract

It is well-established that most pathogens that cause infectious diseases enter the host via mucosal membranes of the respiratory, digestive and genital tracts. Some parenterally administered vaccines induce protection against mucosal pathogens. However, there is increasing evidence that mucosal protection is better afforded by mucosal vaccination, particularly for the induction of memory responses. Mucosal vaccines must pass several difficult hurdles before entering the host and inducing an effective and protective immune response. This review deals with present and past efforts in devising effective mucosal vaccines using delivery systems and immunopotentiating adjuvants for protein-based vaccines. The paper will conclude with the authors' opinion on how the field will or should progress in the future and what will be the required components of ideal future mucosal vaccines that can induce immunological memory.

Approaches to Tuberculosis Mucosal Vaccine Development Using Nanoparticles and Microparticles: A Review

“…75 91-93 In order to efficiently stimulate innate responses and to evoke adaptive immune responses, without disturbing mucosal homeostasis or inducing immunological tolerance, mucosal vaccines must be carefully designed. 94 Different strategies can be used to target the appropriate mucosal site. The development of improved antigen delivery systems, suitable for mucosal routes of immunization while protecting the antigen from degradation during delivery, should provide antigen access to APCs at the induction site, therefore, facilitating mucosal vaccine development.…”

“…206 207 The use of nontoxic adjuvants for mucosal delivery has also been under consideration for intranasal delivery, including the most commonly used Eurocine L3, V. cholerae cholera toxin and Escherichia coli heatlabile enterotoxin. These mucosal adjuvants have been tested in animal models in combination with novel TB vaccine candidates, 94 102 105 208 209 some of which have been evaluated by oral administration, 201 210-213 or intranasally. 13 17 203 214-217 Intranasal booster vaccination of mice with an Ag85B-ESAT-6 fusion protein administered with LTK63 adjuvant, a modified form of E. coli LT, generated strong and persistent Th1 responses and significant protection against M. tuberculosis challenge, reducing bacterial growth by nearly tenfold in lung and spleen tissues.…”

Host-Pathogen Interactions in Streptococcal Diseases

“…While CTB is not approved for human use it is one of the most commonly employed adjuvants for assessing vaccine potential at mucosal surfaces in animal models. However, of these novel adjuvants only liposome vaccine formulations and MPL containing formulations have been approved for clinical use in humans for hepatitis A and influenza and for allergy vaccines, respectively (Ambrosch et al 1997;Vajdy and Singh 2005). Mucosal adjuvants include liposomes (Hall et al 2004), MPL containing formulations (Ulrich 2008;Hall et al 2004), proteosomes (Batzloff et al 2005;Hall et al 2004) and lipid entities Olive et al 2007;Zaman et al 2011).…”

Group A Streptococcal Vaccine Candidates: Potential for the Development of a Human Vaccine

“…Many of these formulations have proved to be effective stimulators of both mucosal and systemic immune responses (Batzloff et al 2005Hall et al 2004;Olive et al 2007;Zaman et al 2011), and some have been shown to protect against mucosal GAS infection (Ulrich 2008;Batzloff et al 2005Batzloff et al , 2006Hall et al 2004;Olive et al 2007). However, of these novel adjuvants only liposome vaccine formulations and MPL containing formulations have been approved for clinical use in humans for hepatitis A and influenza and for allergy vaccines, respectively (Ambrosch et al 1997;Vajdy and Singh 2005).…”