Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination

• DOI: 10.1073/pnas.1606050113
• Publication Date: 2016-10-05T02:29:29Z
• Authors: Hok Hei Tam; Mariane B. Melo; Myungsun Kang; Jeisa M. Pelet; Vera M. Ruda; Maria H. Foley; Joyce K. Hu; Sudha Kumari; Jordan Crampton; Alexis D. Baldeon; Rogier W. Sanders; John P. Moore; Shane Crotty; Robert Langer; Daniel G. Anderson; Arup K. Chakraborty; Darrell J. Irvine
• Keywords: AIDS Vaccines; 0301 basic medicine; B-Lymphocytes; Antibody Affinity; CHO Cells; Infusion Pumps, Implantable; HIV Envelope Protein gp120; Antibodies, Viral; Germinal Center; Drug Administration Schedule; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Cricetulus; HEK293 Cells; Immunogenicity, Vaccine; Lipid A; Adjuvants, Immunologic; Osmotic Pressure; Animals; Humans; Female

Significance We explored the effect of nontraditional vaccine dosing profiles on antibody titers of vaccines and discovered that certain dosing profiles demonstrate >10-fold higher antibody production than the traditional single-dose prime–boost method. We also present a computational model that captures the experimental results and provides a mechanistic understanding of the biology behind the effectiveness of our strategy. This work has clinical significance in vaccine design because it is a simple method to increase the efficacy of subunit vaccines, which may lead to the development of efficacious vaccines for diseases such as HIV.