Probing the Adjuvants

One of the intriguing questions raised by the RV144 AIDS vaccine trial in Thailand, which demonstrated historic though modest (31.2%) vaccine-induced protection from HIV, was whether the protective effect of the vaccine candidates waned over time. Data showed that vaccine efficacy was nearly 60% during the first year following vaccination, but because the trial was not designed to look at whether a certain number of injections were effective or if the protective responses waned with time, investigators were unable to draw any conclusions about this observation (see Raft of Results Energizes Researchers, IAVI Report, Sep.-Oct. 2009).

The regimen used in the RV144 trial consisted of a canarypox vector-based candidate ALVAC-HIV (vCP1521) in a prime-boost combination with AIDSVAX B/E, a genetically engineered version of HIV’s gp120 surface protein. While the adjuvant alum was used in the AIDSVAX boost, Robert Seder, chief of the cellular immunology section at the Vaccine Research Center (VRC) at the US National Institute of Allergy and Infectious Diseases, said that some have wondered whether the results of the trial would have been helped by additional boosting and if so, which adjuvants would be the best ones to use to improve the performance of DNA-based vaccines.

Seder, part of a quartet of speakers during the final day of talks at the Fifteenth Annual Conference on Vaccine Research that spoke about the burgeoning field of vaccine adjuvants, said ongoing studies in a cohort of 54 nonhuman primates have been ranking the performance of adjuvants in improving cellular and humoral immune responses to HIV Env (see A Vaccine's Little Helper, IAVI Report, May-June 2011). The list includes the commonly used alum—which has a long history in vaccine development—as well as lesser-known products like poly-ICLC, a synthetic double-stranded RNA that binds to a toll-like receptor (TLR). The animals were immunized four times over a two-year period.

Perhaps the most telling finding from the measurement of humoral immune responses was that the animals that were given an adjuvant other than alum maintained stable titers over 80 weeks, while the titers in the HIV Env-only arm or HIV Env and alum arm went up and down between the boosts. “You get remarkably better [antibody] binding titer than alum alone,” said Seder.

Seder said separate studies conducted by Duke University researcher Georgia Tomaras found that animals given a vaccine candidate containing the MF59 adjuvant had better mucosal Immunoglobulin G responses.

In an earlier talk about how vaccine adjuvants work, Philippa Marrack, an immunologist in the departments of biochemistry and molecular biology, immunology and medicine at the University of Colorado Health Sciences Center in Denver, described recently published work from her lab showing how mice immunized with ovalbumin and alum activated CD8+ T cells that developed into long-living memory cells that protected the mice following influenza challenge (Proc. Natl. Acad. Sci. 108, 7914, 2011; see An Immunological Rationale for Vaccines, IAVI Report, Nov.-Dec. 2010). “We know the effects of alum on CD4+ T cells, but this was surprising,” said Marrack.