TY - JOUR
T1 - DNA and protein co-immunization improves the magnitude and longevity of humoral immune responses in macaques
AU - Jalah, Rashmi
AU - Kulkarni, Viraj
AU - Patel, Vainav
AU - Rosati, Margherita
AU - Alicea, Candido
AU - Bear, Jenifer
AU - Yu, Lei
AU - Guan, Yongjun
AU - Shen, Xiaoying
AU - Tomaras, Georgia D.
AU - LaBranche, Celia
AU - Montefiori, David C.
AU - Prattipati, Rajasekhar
AU - Pinter, Abraham
AU - Bess, Julian
AU - Lifson, Jeffrey D.
AU - Reed, Steven G.
AU - Sardesai, Niranjan Y.
AU - Venzon, David J.
AU - Valentin, Antonio
AU - Pavlakis, George N.
AU - Felber, Barbara K.
PY - 2014/3/13
Y1 - 2014/3/13
N2 - We tested the concept of combining DNA with protein to improve anti-HIV Env systemic and mucosal humoral immune responses. Rhesus macaques were vaccinated with DNA, DNA&protein co-immunization or DNA prime followed by protein boost, and the magnitude and mucosal dissemination of the antibody responses were monitored in both plasma and mucosal secretions. We achieved induction of robust humoral responses by optimized DNA vaccination delivered by in vivo electroporation. These responses were greatly increased upon administration of a protein boost. Importantly, a co-immunization regimen of DNA&protein injected in the same muscle at the same time induced the highest systemic binding and neutralizing antibodies to homologous or heterologous Env as well as the highest Env-specific IgG in saliva. Inclusion of protein in the vaccine resulted in more immunized animals with Env-specific IgG in rectal fluids. Inclusion of DNA in the vaccine significantly increased the longevity of systemic humoral immune responses, whereas protein immunization, either as the only vaccine component or as boost after DNA prime, was followed by a great decline of humoral immune responses overtime. We conclude that DNA&protein co-delivery in a simple vaccine regimen combines the strength of each vaccine component, resulting in improved magnitude, extended longevity and increased mucosal dissemination of the induced antibodies in immunized rhesus macaques.
AB - We tested the concept of combining DNA with protein to improve anti-HIV Env systemic and mucosal humoral immune responses. Rhesus macaques were vaccinated with DNA, DNA&protein co-immunization or DNA prime followed by protein boost, and the magnitude and mucosal dissemination of the antibody responses were monitored in both plasma and mucosal secretions. We achieved induction of robust humoral responses by optimized DNA vaccination delivered by in vivo electroporation. These responses were greatly increased upon administration of a protein boost. Importantly, a co-immunization regimen of DNA&protein injected in the same muscle at the same time induced the highest systemic binding and neutralizing antibodies to homologous or heterologous Env as well as the highest Env-specific IgG in saliva. Inclusion of protein in the vaccine resulted in more immunized animals with Env-specific IgG in rectal fluids. Inclusion of DNA in the vaccine significantly increased the longevity of systemic humoral immune responses, whereas protein immunization, either as the only vaccine component or as boost after DNA prime, was followed by a great decline of humoral immune responses overtime. We conclude that DNA&protein co-delivery in a simple vaccine regimen combines the strength of each vaccine component, resulting in improved magnitude, extended longevity and increased mucosal dissemination of the induced antibodies in immunized rhesus macaques.
UR - http://www.scopus.com/inward/record.url?scp=84898716198&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84898716198&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0091550
DO - 10.1371/journal.pone.0091550
M3 - Article
C2 - 24626482
AN - SCOPUS:84898716198
SN - 1932-6203
VL - 9
JO - PloS one
JF - PloS one
IS - 3
M1 - e91550
ER -