NEW YORK (GenomeWeb) – A study published online today in Science Translational Medicine suggests the presence or absence of certain human leukocyte antigen class II gene variants can help predict whether vaccination will protect against HIV.
Based on immune system responses identified during RV144 — an HIV vaccine clinical trial conducted in Thailand — an international team led by investigators at the Walter Reed Army Institute of Research's US Military HIV Research Program did HLA class II genotyping on 760 vaccinated or unvaccinated individuals with or without HIV to search for variants related to vaccine protection and related antibody profiles.
The analysis uncovered variants in the HLA genes DQB1 and DPB1 that were linked to higher- or lower-than-usual risk of HIV infection, respectively, following vaccination — effects that were intertwined with downstream differences in the type of antibodies produced in response to vaccination.
"We found that antibody responses correlated with increased or decreased risk of acquiring HIV only in the presence of specific host HLA alleles," senior author Rasmi Thomas, a researcher with the Walter Reed Army Institute and the Henry M. Jackson Foundation for the Advancement of Military Medicine, said in a statement.
During the first 42 months of the RV144 phase 3 vaccine trial, the team found that the vaccine was roughly 31 percent effective in preventing HIV infection. But this protection did not appear to be uniform.
Instead, subsequent research revealed that individuals who produced large numbers of immunoglobulin A antibodies aimed at an HIV envelope protein after vaccination tended to have slightly lower protection from the virus. On the other hand, those who bumped up their output of immunoglobulin G antibodies that target a portion of the same Env protein after vaccination seemed somewhat more protected.
To delve into the host genetic factors contributing to this effect, authors of the new analysis focused on HLA class II genes — polymorphic genes coding for DR, DQ, and DP molecules that make their way to the surface of antigen-producing cells and set off a cascade of events that ultimately prompts B cells to produce antibodies.
Given the contribution that these HLA class II genes make to humoral immune responses, including those prompted by vaccination, the team reasoned that variation in these genes might account for some of the variable immune responses described in individuals who received vaccination against HIV.
Using sequencing-based genotyping, the researchers assessed HLA class II gene variation in 41 vaccinated individuals who, nonetheless, became infected with HIV, and 205 uninfected, vaccinated controls, focusing on 31 alleles found with frequencies of at least 5 percent each.
They did similar testing on 67 infected individuals who received placebos and 450 uninfected placebo recipients.
The team's results confirmed the enhanced risk of infection found in vaccinated individuals with high levels of immunoglobulin A. But this effect seemed to be specific for those who carried a particular version of a DQB1 allele called DQB1*06.
For vaccinated individuals who had a version of the DPB1 gene known as DPB1*13, on the other hand, the researchers saw elevated levels of the HIV envelope-targeting immunoglobulin G antibody linked to increased vaccine protection in the past.
Indeed, HIV vaccination appeared to be far more effective in individuals with both DPB1*13 and bumped up levels of certain immunoglobulin G antibodies: the team estimated RV144 vaccine efficacy at around 71 percent of individuals in that group.
Co-author Colonel Nelson Michael, director of the US Military HIV Research Program, said the current findings underscore the importance of taking host genetics into account when interpreting the vaccine trial data and designing other HIV vaccines.