Immune correlate–guided vaccine development
Vaccines are among the most cost-effective and efficacious public health interventions that prevent disease at a global level. While traditional vaccine design approaches, focused on weakening or inactivating the pathogen or designer antigens, have consistently failed to provide protection against some of the deadliest pathogens in both animal models and human vaccine studies, the concept of “rational vaccine design” has emerged. This concept hinges on the identification of the antibody functions that are associated with vaccine-induced immunity, which are then used to reverse engineer the immune response such that the targeted functions are elicited via vaccination. Two pieces of knowledge are critical to this vaccine design approach, termed immune correlate–guided vaccine design: the identification and validation of the immune correlates themselves and understanding how the immune response is altered by changes in the vaccine itself.
Rational vaccine design: Modifying antibody functionality with adjuvants
As vaccine design becomes more sophisticated, more attributes become available to tune the resulting immune response. Changes in the vaccination strategy and vaccine regimen, including changes to vaccine dose and timing, and the inclusion of specific adjuvants have all been shown to impact the subsequent immune response. Just as Systems Serology can be used to rapidly identify and validate the actual correlates of protection, Systems Serology can also be used to screen novel vaccine candidates to identify those with the target functional profile. Building on immune correlates identified across various candidate HIV vaccines, Systems Serology was used to characterize the functional activity of a panel of HIV vaccine candidates to determine which vaccine regimen best induced the target functional profile.
Systems Serology Application:
As part of this study, participants received one of eight different vaccine regimens that differed in the composition and dose of the vaccine boosts. While each of the regimens induced HIV-specific antibodies, the functional activity that was elicited was dramatically different across vaccine regimens. While some vaccine regimens induced low levels of antibody-dependent cellular phagocytosis (the target antibody function), other vaccine regimens induced high levels of antibody-dependent cellular phagocytosis. Intriguingly, the increased functional activity was not solely the result of increased antibody levels, suggesting that changes in vaccine regimen can not only impact antibody quantity but can also independently alter antibody quality.
Rational vaccine design: Modifying antibody functionality via changes in vaccine regimen
Reprinted from The Lancet, 392, Barouch, DH, et al., Evaluation of a Mosaic HIV-1 Vaccine in a Randomized, Double-Blinded, Placebo-Controlled Phase I/IIa Clinical Trial and in Rhesus Monkeys, 232-243, 2018, with permission from Elsevier.
When evaluating new vaccines for clinical development, neutralization is often the experimental assay used to predict the potential efficacy of a vaccine candidate, regardless of whether neutralization is known to be the correlate of protection. However, the importance of extra-neutralizing antibody functions, such as antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, and antibody-dependent complement deposition, in providing protection from infection following vaccination is becoming increasingly apparent. The Systems Serology suite of assays offered by SeromYx provides a platform in which numerous antibody functions can be rapidly evaluated, providing critical information for the selection of the optimal vaccine regimens that should move further into clinical development.
Francica JR, et al., Innate transcriptional effects by adjuvants on the magnitude, quality, and durability of HIV envelope responses in NHPs. Blood Adv. 2017 Nov 28; 1(25): 2329–2342.
Barouch DH, et al., Evaluation of a mosaic HIV 1 vaccine in a multicentre randomised double blind placebo controlled phase 1 2a clinical trial APPROACH and in rhesus monkeys. Lancet. 2018 Jul 21; 392(10143): 232–243.