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Predicting vaccine antibody responses

New EAVI2020 research published in Cell Reports Medicine has found that early innate immune responses can be used to predict the neutralising antibody responses in vaccinated macaques.

The study indicates that monitoring immune signatures during early vaccine development could assist in identifying biomarkers that predict vaccine efficacy.

“Our aim when we did this study was to find some early predictive markers to decrease the risk of failure at a later stage in vaccine development,” said Dr Nathalie Bosquet from the Commissariat à l’Energie Atomique et aux Energies Alternatives (CEA) in Paris.

“You usually find out if a vaccine appears effective during human clinical trials, which is quite late in the development of a vaccine. It can sometimes be as late as stage 3 clinical trials, which can involve thousands of participants.”

Lowering the risk of failure

Developing new HIV vaccine candidates requires long-term effort and investment with a high risk of failure at advanced stages.

Given the time and resources invested in clinical trials, innovative prediction methods are needed to decrease late-stage failure in vaccine development.

Vaccine development failure can result from our poor understanding of immune mechanisms of protection following immunisation, as only a few immune parameters are assessed during early-stage efficacy trials.

Innate immunity is one of the first players in shaping the vaccine-induced immune responses, and molecular and cellular changes immediately following vaccine injection may help to identify markers predicting the later adaptive response.

Such predictive signals would be particularly useful to accelerate the selection of the most promising vaccine candidates at early developmental stages.

Hunting for a predictive marker

In their search for these predictive markers, the team studied early immune responses in HIV-Env SOSIP- immunised cynomolgus macaques, comparing combinations of different adjuvants for vaccination and different routes of administration. Both adjuvants and administration routes are known to influence the quality of the innate immune response and, ultimately, the adaptive immune response.

Overall, the study demonstrated that subsets of myeloid cells, a type of immune cell, differ depending on the given adjuvant and immunisation route. Moreover, they identified a set of cell markers that correlates with vaccine-induced neutralizing antibody activity that could be used to develop models that predict the quality of the vaccine response.

The next steps for this research will be to assess how the vaccines tested in this study fair in human trials, some of which are already taking place as part of EAVI2020, to see if the observations corroborate these findings.

If the findings from this study are validated, the hope is that the technique could be routinely used in vaccine development to screen candidates at an early stage, lowering the risk of failure later on in development.

This could save both time and money and allow researchers to focus their efforts on more promising vaccine candidates.

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