Identifying correlates of protection

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Context:

The need for vaccines against some of the world’s deadliest pathogens, including HIV, malaria, TB, and influenza, has never been greater. While measurement of antibody quantities provides a cursory impression of the overall magnitude of the antibody response, by themselves, this information provides little insight into the mechanism by which antibodies provide protection from infection, information that is likely critical for the development of an effective vaccine. Systems Serology was developed to overcome this limitation, allowing for the rapid definition of the functional and biophysical profiles of the antibody response, which is key to mechanistically understanding how antibodies provide protection following vaccination and identifying a correlate of protection.

Identifying correlates of protection following natural infection or vaccination
Identifying correlates of protection following natural infection or vaccination

Problem:

While over 100 vaccines against HIV have been tested in clinical trials over the last 30 years, only one vaccine has demonstrated any degree of efficacy—efficacy that could not be replicated in follow-up trials. However, while human trials have repeatedly failed to demonstrate protection, promising vaccine candidates that are protective in animal models have been developed. Understanding how these candidate vaccines are protective in animal models potentially provides a road map for the strategic development of a vaccine that is protective in humans. Focusing on one such vaccine candidate, Systems Serology was applied to identify the functional features of the vaccine-elicited antibody response that were tied to protection.

Systems Serology Application:

Protective Efficacy of a Global HIV1 Mosaic Vaccine against Heterologous SHIV Challenges in Rhesus Monkeys
Protective Efficacy of a Global HIV-1 Mosaic Vaccine against Heterologous SHIV Challenges in Rhesus Monkeys

Of the antibody features and functions that were examined, several were linked with protection from infection, including antibody titer and neutralization activity. Beyond titer and neutralization, however, antibody-dependent cellular phagocytosis, that is, the ability of an antibody to drive internalization and degradation of antibody-coated targets by monocytes and macrophages, was also linked with protection. This finding suggests that antibody functions other than neutralization may be critical for driving protection. As only low levels of neutralizing antibodies were generated by the tested vaccine, the extra-neutralizing activity of antibodies may be necessary for vaccine-mediated protection, especially against difficult-to-neutralize viruses like HIV.


Conclusion:

The results of the Systems Serology profiling of candidate HIV vaccines suggest that we may be overlooking the potential role of extra-neutralizing antibody functions in driving protection. The identification of the antibody functions—both neutralization as well as extra-neutralizing antibody functions—associated with protection from infection, will ultimately allow for the development and optimization of candidate vaccines that drive high levels of these specific functions, potentially increasing the efficacy of the vaccine. The Systems Serology platform offered by SeromYx can be used to identify antibody features and functions that are critical for vaccine-mediated protection, providing the information necessary to develop more effective vaccines.

References

Barouch DH, et al., Protective efficacy of adenovirus/protein vaccines against SIV challenges in rhesus monkeys. Science. 2015 Jul 17; 349(6245): 320–324.

updated: 2 months ago