The new first-line defense: the potential of nasopharyngeal colonization in vaccine strategies

Abstract:

Pathogens that can colonize the upper respiratory tract include Streptococcus pneumoniae, Hemophilus influenzae, Neisseria meningitidis, Moraxella catarrhalis, and Staphylococcus aureus. While these pathogens commonly asymptomatically colonize the nasopharynx of healthy adults, disease progression may occur in some individuals. In addition to these respiratory pathogens, there are a large number of commensal species also found in the upper respiratory tract which only very rarely cause disease, creating a complex community of bacterial species in the nasopharynx. This review addresses the novel, potential strategies that utilize the interactions between both homologous and heterologous species in the nasopharynx to vaccinate individuals against pathogenic bacteria. These strategies include the mechanisms employed by colonizing bacteria to regulate the presence of other species in the nasopharynx and the effect that colonization of the nasopharynx has on the host immune response. Interventional strategies investigated so far include the introduction of nonpathogenic bacteria to the nasopharynx to immunize against a closely related species, controlled colonization using both wild-type and attenuated species, and the use of other nonpathogenic colonizers to express antigens from potential pathogens. All these approaches harness the ability of the colonization to induce a mucosal immune response that can protect against future infection. In this review, S. pneumoniae and N. meningitidis colonization are used as case studies for this approach as the immunological effects of colonization have been widely studied in animal and human models. Colonization-based strategies have great potential, and, in particular, the attenuated strain approach has produced some encouraging data in animal models. However, the strategy for attenuating virulence must be stringent and caused by highly stable mutations that are unlikely to revert. In addition, the consequences of artificial administration of genetically modified bacteria to the nasopharynx on the usual host microbiome are unknown and would need to be monitored carefully.

Keywords::

• Streptococcus pneumoniae
• colonization
• adaptive immunity
• antibody
• protein antigen
• capsular antigen
• Neisseria sp.