Email updates

Keep up to date with the latest news and content from Retrovirology and BioMed Central.

This article is part of the supplement: AIDS Vaccine 2012

Open Access Poster presentation

Vector induced skewing of antibody Fc-effector functions

A Chung1*, A Dugast1, H Robinson1, Y Chan1, ME Ackerman2, J Cox3, W Koff3, D Barouch4, S Rerks-Ngarm5, N Michael6, J Kim6 and G Alter1

  • * Corresponding author: A Chung

Author Affiliations

1 Ragon Institute of MGH, MIT & Harvard, Boston, MA, USA

2 Thayer School of Engineering, Dartmouth,, Hanover, NH, USA

3 International AIDS Vaccine Initiative, New York, NY, USA

4 Beth Israel Deaconess Medical Center, Boston, MA, USA

5 Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand

6 US Military HIV Research Program, Silver Spring, MD, USA

For all author emails, please log on.

Retrovirology 2012, 9(Suppl 2):P361  doi:10.1186/1742-4690-9-S2-P361

The electronic version of this article is the complete one and can be found online at: http://www.retrovirology.com/content/9/S2/P361


Published:13 September 2012

© 2012 Chung et al; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background

The RV144 vaccine showed a moderate efficacy of protection from HIV infection. The major immune response induced by RV144 was non-neutralizing HIV-specific antibodies (Abs), that may have potentially mediated Ab Dependent Cellular Cytotoxicity (ADCC) and/or Ab dependent Cellular Phagocytosis (ADCP). However little is known about the potential role of different vaccine regimens on inducing these types of humoral immune responses, and whether particular vaccine approaches may preferentially induce robust innate immune recruiting antibody activity that could confer more protection against infection. We therefore aimed to characterize the antibody-effector functional profiles of antibodies elicited by a number of different vaccine approaches including those induced in the: VAX003 trial (bivalent rgp120 clade B/E), RV144 (ALVAC vCP1521 + rgp120 B/E), IPCAVD001 (rAd26.ENVA.01), IAVI-C002 (MVA), IAVI-P002 (DNA + MVA) and IAVI-V001 (DNA + rAd5).

Methods

Abs were purified from the plasma or serum of vaccinees. IgGs were then assayed for ADCC, ADCP, NK degranulation and cytokine production, antibody isotype selection, and Ab affinity for Fc-receptors ( FcγRIIa, FcγRIIb and FcγRIIIa).

Results

IAVI-C002 and IAVI-P002 vaccination induced negligible Fc-mediated innate immune responses, while IAVI-V001 was able to induce ADCP in 33% of vaccines. IPCAVD001 was also able to induce strong ADCP in 90% of subjects, but only weak ADCC, NK degranulation or cytokine release. Interestingly, only RV144 and VAX003 vaccination induced strong ADCC, ADCP, NK degranulation and cytokine responses. Furthermore, Abs induced by RV144 and IPCAVD exhibited a more polyfunctional profile compared to VAX003, associated with a skewed isotype distribution of HIV-specific Abs and selective Fc-receptor affinity binding profile.

Conclusion

These data suggest for the first time that distinct vaccine regimens, and vaccine vectors, may selectively induce antibodies with Fc-enhanced functional profiles able to elicit polyfunctional antibody responses, that may provide improved protection from infection.