Strategies to Improve Vaccines for the Neonate - Novel vaccine formulations can provide more effective immune protection to newborns. - BioPharm International

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Strategies to Improve Vaccines for the Neonate
Novel vaccine formulations can provide more effective immune protection to newborns.


BioPharm International


Mucosal Vaccination

Because most invading pathogens enter the host via the mucosal surfaces, induction of strong mucosal immunity is often crucial for disease protection.52 Prime examples of such infections include gastrointestinal infections with enterotoxigenic E. coli (ETEC), rotavirus, or calicivirus, and respiratory infections with Mycoplasma, influenza virus, or respiratory syncytial virus. Effective vaccines therefore need to target the mucosa-associated lymphoid tissues (MALT), ideally at the potential site of infection. The MALT represent the largest immune compartment in the body and is required to (1) protect the mucosal membranes against infection; (2) to tolerate antigens derived from ingested food, airborne matter, and commensal microorganisms; and (3) to prevent the development of any potentially harmful immune responses against these antigens in case they breach the mucosal lining.52 To induce strong mucosal immune responses vaccines must be delivered to the mucosal site, where the vaccine antigen is taken up by either M cells, dendritic cells, or epithelial cells and subsequently passed on to antigen presenting cells. Subsequently, these cells migrate into specialized tissues such as Peyer's patches, lymph nodes, and tonsils, in which the antigen is presented to effector cells of the immune system. During this process the effector cells are imprinted to home back to the mucosal surfaces, a process mediated by interaction between locally expressed chemokines and integrins and chemokine receptors found on the surface of the effector cells. It is this interaction that allows effector cells to specifically home to the site of induction. For example, expression of the chemokine CCL25 and recognition by the chemokine receptor CCR9 allow specific homing to the small intestinal mucosa. This demonstrates the importance of delivering future vaccines by the mucosal surfaces. Delivery systems and effective mucosal adjuvants are needed that not only facilitate delivery of the vaccine to mucosal sites, but also enhance antigen uptake and provide a pro-inflammatory environment resulting in recruitment and activation of immune cells.

Conclusions

Vaccines are the most effective means of controlling infectious diseases. Novel approaches have been developed to improve existing vaccines and to develop novel vaccines. In this regard, adding of potent adjuvants that link innate and acquired immunity as well as delivery systems for mucosal delivery that eliminate the risk of needles, are promising approaches to make vaccines more effective in humans and animals. The development of vaccines for the newborn will greatly benefit from these novel technologies, as immunization of the newborn has proven to be a major challenge for today's vaccines.

Acknowledgements

Funding in the investigators' laboratories was provided by a grant through the Grand Challenges in Global Health Initiative by the Bill and Melinda Gates Foundation, the Krembil Foundation, the Canadian Institutes for Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), the Saskatchewan Health Research Foundation (SHRF), and the Agriculture Development Fund Saskatchewan (ADF Saskatchewan). Published with permission of the Director of the Vaccine & Infectious Disease Organization as article number 480.

VOLKER GERDTS is an associate director and GEORGE MUTWIRI is a program manager at Vaccine & Infectious Disease Organization Saskatoon, Canada, +1.306.966.1513,

References

1. Janeway CA Jr., Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002(20):197–216.

2. Athman R, Philpott D. Innate immunity via Toll-like receptors and Nod proteins. Curr Opin Microbiol, 2004(7):25–32.

3. Trinchieri G, Sher A. Cooperation of Toll-like receptor signals in innate immune defence. Nat Rev Immunol. 2007(7):179–190.

4. Hoebe K, Janssen,E, Beutler B. The interface between innate and adaptive immunity. Nat Immunol. 2004(5):971–974.

5. Finlay BB, Hancock RE. Can innate immunity be enhanced to treat microbial infections? Nat Rev Microbiol. 2004(2):497–504.

6. Elahi S, et al. Infection of newborn piglets with Bordetella pertussis: a new model for pertussis. Infect Immun. 73, 459:3636–3645.


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