Editors' ChoiceVaccines

The right adjuvant gives T follicular helper cells a boost

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Science Translational Medicine  19 Jun 2019:
Vol. 11, Issue 497, eaax9565
DOI: 10.1126/scitranslmed.aax9565

Abstract

The vaccine adjuvant GLA-SE increases the magnitude and longevity of antibody responses by increasing the quantity of T follicular helper cells in humans.

Vaccination is a key control strategy for many infectious diseases. However, effective vaccination strategies are lacking for some of the globe’s most important diseases, such as HIV and malaria. Many vaccines function by inducing high titers of long-lived antibodies against the pathogens. As such, strategies to boost the quantity and longevity of antibody responses may improve vaccine efficacy.

Hill et al. investigated the ability of the adjuvant glucopyranosyl lipid adjuvant–stable emulsion (GLA-SE) to improve vaccine-induced responses to a Plasmodium falciparum malaria antigen in malaria–pre-exposed adults. They focused on T follicular helper (TFH) cells, which are critical in driving B cell maturation and antibody development. Although TFH cells localize and function within the germinal centers—a site not readily accessible in human studies—peripheral circulating counterparts have been identified, which allows the study of TFH in human blood samples.

In comparison with the widely used adjuvant Alum, the GLA-SE adjuvant formulation induced a higher magnitude and greater longevity of antimalarial antibodies. This enhanced antibody induction was associated with an increase in activated circulating TFH (cTFH) cells following vaccination in GLA-SE recipients. GLA-SE administration was also associated with an expansion of public TCRβ clonotypes shared between individuals among activated cTFH. Further, GLA-SE was associated with an increased stimulation of extrafollicular antibody secreting cells, suggesting that GLA-SE boosted both short- and long-lived responses. Last, Hill and colleagues show that a specific subset of cTFH cells that express CXCR5 and the highest amount of PD1 closely resemble germinal center TFH transcriptionally. This specific subset of cTFH was most strongly associated with antibody induction in both malaria vaccination, as well as in a separate study of influenza vaccination.

Together, this work not only identifies a specific subset of cTFH cells within the readily accessible blood compartment of humans that could potentially be used as a surrogate for germinal center responses but also highlights a key role of adjuvant selection in improving vaccine efficacy. Currently, the only licensed antimalarial vaccine demonstrates a short-lived efficacy of ~35%. This study highlights the possibility that improved adjuvants may boost not only the initial but also long-term efficacy of malaria vaccines, and it opens avenues for improved vaccine development in other important human pathogens.

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