Immunoproteomics: The Key to Discovery of New Vaccine Antigens Against Bacterial Respiratory Infections

Abstract

The increase in antibiotic resistance and the shortage of new antimicrobials to prevent difficult bacterial infections underlines the importance of prophylactic therapies to prevent infection by bacterial pathogens. Vaccination has reduced the incidence of many serious diseases, including respiratory bacterial infections. However, there are many pathogens for which no vaccine is available and some vaccines are not effective among all age groups or among immunocompromised individuals. Immunoproteomics is a powerful technique which has been used to identify potential vaccine candidates to protect against pathogenic bacteria. The combination of proteomics with the detection of immunoreactive antigens using serum highlights immunogenic proteins that are expressed during infection. This is particularly useful when patient serum is used as the antigens that promote a humoral response during human infection are identified. This review outlines examples of vaccine candidates that have been identified using immunoproteomics and have successfully protected animals against challenge when tested in immunisation studies. Many immunoreactive proteins are common to several unrelated pathogens, however some of these are not always protective in animal immunisation and challenge studies. Furthermore, examples of well-established immunogens, including Bordetella pertussis antigen FHA were not detected in immunoproteomics studies, indicating that this technology may underrepresent the immunoreactive proteins in a pathogen. Although only one step in the pathway towards an efficacious approved vaccine, immunoproteomics is an important technology in the identification of novel vaccine antigens.

Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection

“…This predictive approach assumes that proteins that are able to induce protective immunity are located outside the cell membrane and therefore possess signal sequences (4). Immunoproteomics has also been used to identify novel antigens that elicit an immune response, as recently reviewed (5), but when used in isolation, it has limitations, and no efficacious antigens have yet been identified by using this approach. Indeed, the confirmed prophylactic Bordetella pertussis antigen filamentous hemagglutinin (FHA), a component of most licensed acellular whooping cough vaccines, was undetectable in two immunoproteomic studies (6,7).…”

Proteome signatures—how are they obtained and what do they teach us?

“…However, there are many pathogens for which there are no vaccines and some are not effective among all demographics, namely age groups and immunocompromised individuals (Dennehy and McClean 2012).…”

“…Combining proteomics with the detection of antigens that show immunoreactivity allows for the identification of immunogenic proteins/ peptides expressed during infection (Dennehy and McClean 2012). Most studies have been focused on either cell surface or outer membrane proteins (Montero et al 2014;Newcombe et al 2014;Wu et al 2008b;Zhou et al 2009), as these are the de facto interface for host-pathogen interactions.…”

“…Most studies have been focused on either cell surface or outer membrane proteins (Montero et al 2014;Newcombe et al 2014;Wu et al 2008b;Zhou et al 2009), as these are the de facto interface for host-pathogen interactions. Additionally, secreted proteins could also be of special interest (Barh et al 2013;Campbell et al 2015;Enany et al 2012;Wang et al 2014b;Wu et al 2008a), as these are also primary antigen targets of the host immune response and include many virulence factors (Dennehy and McClean 2012). Collectively, their exposure to the host immune system marks these sets of proteins as a rich source of vaccine potential candidates.…”

“…Consequently, harnessing the host-pathogen response can be of significance in two distinct and equally key aspects of vaccine development: (a) identification of novel vaccine antigens by determining the immunogenic bacterial proteins from vaccinated, colonized, or convalescing individuals and (b) the enhancement of efficacy of already identified immunogens (Dennehy and McClean 2012). Table 1 summarizes some of the most recent works carried out in both the identification of new antigens as well as on the improvement of identified ones.…”