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Protein-based, but not viral vector alone, HIV vaccine boosting drives an IgG1-biased polyfunctional humoral immune response
Stephanie Fischinger, … , Hendrik Streeck, Galit Alter
Stephanie Fischinger, … , Hendrik Streeck, Galit Alter
Published June 18, 2020
Citation Information: JCI Insight. 2020;5(12):e135057. https://doi.org/10.1172/jci.insight.135057.
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Research Article AIDS/HIV Immunology

Protein-based, but not viral vector alone, HIV vaccine boosting drives an IgG1-biased polyfunctional humoral immune response

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Abstract

The RV144 HIV-1 vaccine trial results showed moderate reduction in viral infections among vaccinees as well as induction of antibody-dependent cellular cytotoxicity and vaccine-specific IgG and IgG3 responses directed at variable loop regions 1 and 2 of the HIV envelope protein. However, with the recent failure of the HVTN 702 clinical trial, comprehensive profiling of humoral immune responses may provide insight for these disappointing results. One of the changes included in the HVTN 702 study was the addition of a late boost, aimed at augmenting peak immunity and durability. The companion vaccine trial RV305 was designed to permit the evaluation of the immunologic impact of late boosting with either the boosting protein antigen alone, the canarypox viral vector ALVAC alone, or a combination of both. Although previous data showed elevated levels of IgG antibodies in both boosting arms, regardless of ALVAC-HIV vector incorporation, the effect on shaping antibody effector function remains unclear. Thus, here we analyzed the antibody and functional profile induced by RV305 boosting regimens and found that although IgG1 levels increased in both arms that included protein boosting, IgG3 levels were reduced compared with the original RV144 vaccine strategy. Most functional responses increased upon protein boosting, regardless of the viral vector-priming agent incorporation. These data suggest that the addition of a late protein boost alone is sufficient to increase functionally potent vaccine-specific antibodies previously associated with reduced risk of infection with HIV.

Authors

Stephanie Fischinger, Sally Shin, Carolyn M. Boudreau, Margaret Ackerman, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Jerome H. Kim, Merlin L. Robb, Nelson L. Michael, Robert J. O’Connell, Sandhya Vasan, Hendrik Streeck, Galit Alter

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Figure 1

AIDSVAX protein boosting alone or in combination with ALVAC drives an IgG1-focused immune profile.

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AIDSVAX protein boosting alone or in combination with ALVAC drives an Ig...
(A) The diagram shows the vaccination schedule of RV144 linked to RV305. RV305 reenrolled healthy RV144 participants and administered 2 boosts of AIDSVAX B/E, ALVAC, or a combination of the two. (B) Spider plots show the relative antibody titers MFIs (z-scored) via Luminex against different vaccine antigens at week 26 for RV144 (blue), combination (maroon), AIDSVAX (orange) and ALVAC (yellow) for IgG1 (left) and IgG3 (right). Each line represents the median of the z-scored values for each vaccine group of the isotype MFI. (C) The dot plots show relative gp120MN-specific antibody level MFIs across the subclasses and isotypes (IgG1, IgG2, IgG3, IgG4, IgA, and IgM). Each dot represents one vaccinee. Data are shown as mean ± SEM. A Kruskal Wallis test was performed to test for statistical differences across groups. *P < 0.05, **P < 0.01, ***P < 0.001, and ****P < 0.0001. The dotted line shows placebo levels.

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ISSN 2379-3708

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