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Impact of adjuvants on the biophysical and functional characteristics of HIV vaccine-elicited antibodies in humans.

Publication ,  Journal Article
Xu, S; Carpenter, MC; Spreng, RL; Neidich, SD; Sarkar, S; Tenney, D; Goodman, D; Sawant, S; Jha, S; Dunn, B; Juliana McElrath, M; Bekker, V ...
Published in: NPJ Vaccines
August 4, 2022

Adjuvants can alter the magnitude, characteristics, and persistence of the humoral response to protein vaccination. HIV vaccination might benefit from tailored adjuvant choice as raising a durable and protective response to vaccination has been exceptionally challenging. Analysis of trials of partially effective HIV vaccines have identified features of the immune response that correlate with decreased risk, including high titers of V1V2-binding IgG and IgG3 responses with low titers of V1V2-binding IgA responses and enhanced Fc effector functions, notably antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). However, there has been limited opportunity to compare the effect of different adjuvants on these activities in humans. Here, samples from the AVEG015 study, a phase 1 trial in which participants (n = 112) were immunized with gp120SF-2 and one of six different adjuvants or combinations thereof were assessed for antibody titer, biophysical features, and diverse effector functions. Three adjuvants, MF59 + MTP-PE, SAF/2, and SAF/2 + MDP, increased the peak magnitude and durability of antigen-specific IgG3, IgA, FcγR-binding responses and ADCP activity, as compared to alum. While multiple adjuvants increased the titer of IgG, IgG3, and IgA responses, none consistently altered the balance of IgG to IgA or IgG3 to IgA. Linear regression analysis identified biophysical features including gp120-specific IgG and FcγR-binding responses that could predict functional activity, and network analysis identified coordinated aspects of the humoral response. These analyses reveal the ability of adjuvants to drive the character and function of the humoral response despite limitations of small sample size and immune variability in this human clinical trial.

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Published In

NPJ Vaccines

DOI

EISSN

2059-0105

Publication Date

August 4, 2022

Volume

7

Issue

1

Start / End Page

90

Location

England

Related Subject Headings

  • 3207 Medical microbiology
  • 3204 Immunology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Xu, S., Carpenter, M. C., Spreng, R. L., Neidich, S. D., Sarkar, S., Tenney, D., … Ackerman, M. E. (2022). Impact of adjuvants on the biophysical and functional characteristics of HIV vaccine-elicited antibodies in humans. NPJ Vaccines, 7(1), 90. https://doi.org/10.1038/s41541-022-00514-9
Xu, Shiwei, Margaret C. Carpenter, Rachel L. Spreng, Scott D. Neidich, Sharanya Sarkar, DeAnna Tenney, Derrick Goodman, et al. “Impact of adjuvants on the biophysical and functional characteristics of HIV vaccine-elicited antibodies in humans.NPJ Vaccines 7, no. 1 (August 4, 2022): 90. https://doi.org/10.1038/s41541-022-00514-9.
Xu S, Carpenter MC, Spreng RL, Neidich SD, Sarkar S, Tenney D, et al. Impact of adjuvants on the biophysical and functional characteristics of HIV vaccine-elicited antibodies in humans. NPJ Vaccines. 2022 Aug 4;7(1):90.
Xu, Shiwei, et al. “Impact of adjuvants on the biophysical and functional characteristics of HIV vaccine-elicited antibodies in humans.NPJ Vaccines, vol. 7, no. 1, Aug. 2022, p. 90. Pubmed, doi:10.1038/s41541-022-00514-9.
Xu S, Carpenter MC, Spreng RL, Neidich SD, Sarkar S, Tenney D, Goodman D, Sawant S, Jha S, Dunn B, Juliana McElrath M, Bekker V, Mudrak SV, Flinko R, Lewis GK, Ferrari G, Tomaras GD, Shen X, Ackerman ME. Impact of adjuvants on the biophysical and functional characteristics of HIV vaccine-elicited antibodies in humans. NPJ Vaccines. 2022 Aug 4;7(1):90.

Published In

NPJ Vaccines

DOI

EISSN

2059-0105

Publication Date

August 4, 2022

Volume

7

Issue

1

Start / End Page

90

Location

England

Related Subject Headings

  • 3207 Medical microbiology
  • 3204 Immunology