Abstract
Dominant antibody responses in vaccinees who received the HIV-1 multiclade (A, B, and C) envelope (Env) DNA/recombinant adenovirus virus type 5 (rAd5) vaccine studied in HIV-1 Vaccine Trials Network (HVTN) efficacy trial 505 (HVTN 505) targeted Env gp41 and cross-reacted with microbial antigens. In this study, we asked if the DNA/rAd5 vaccine induced a similar antibody response in rhesus macaques (RMs), which are commonly used as an animal model for human HIV-1 infections and for testing candidate HIV-1 vaccines. We also asked if gp41 immunodominance could be avoided by immunization of neonatal RMs during the early stages of microbial colonization. We found that the DNA/rAd5 vaccine elicited a higher frequency of gp41-reactive memory B cells than gp120-memory B cells in adult and neonatal RMs. Analysis of the vaccine-induced Env-reactive B cell repertoire revealed that the majority of HIV-1 Env-reactive antibodies in both adult and neonatal RMs were targeted to gp41. Interestingly, a subset of gp41- reactive antibodies isolated from RMs cross-reacted with host antigens, including autologous intestinal microbiota. Thus, gp41-containing DNA/rAd5 vaccine induced dominant gp41-microbiota cross-reactive antibodies derived from blood memory B cells in RMs as observed in the HVTN 505 vaccine efficacy trial. These data demonstrated that RMs can be used to investigate gp41 immunodominance in candidate HIV-1 vaccines. Moreover, colonization of neonatal RMs occurred within the first week of life, and immunization of neonatal RMs during this time also induced a dominant gp41-reactive antibody response.
| Original language | English (US) |
|---|---|
| Article number | e00923-17 |
| Journal | Journal of virology |
| Volume | 91 |
| Issue number | 21 |
| DOIs | |
| State | Published - Nov 1 2017 |
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Keywords
- Gp41
- HIV-1 envelope
- HIV-1 vaccine
- Microbiome
- Rhesus macaques
ASJC Scopus subject areas
- Microbiology
- Immunology
- Insect Science
- Virology
Cite this
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HIV DNA-adenovirus multiclade envelope vaccine induces gp41 antibody immunodominance in rhesus macaques. / Han, Qifeng; Williams, Wilton B.; Saunders, Kevin O.; Seaton, Kelly E.; Wiehe, Kevin J.; Vandergrift, Nathan; Von Holle, Tarra A.; Trama, Ashley M.; Parks, Robert J.; Luo, Kan; Gurley, Thaddeus C.; Kepler, Thomas B.; Marshall, Dawn J.; Montefiori, David C.; Sutherland, Laura L.; Alam, Munir S.; Whitesides, John F.; Bowman, Cindy M.; Permar, Sallie R.; Graham, Barney S.; Mascola, John R.; Seed, Patrick C.; Van Rompay, Koen K.A.; Tomaras, Georgia D.; Moody, M. Anthony; Haynes, Barton F.
In: Journal of virology, Vol. 91, No. 21, e00923-17, 01.11.2017.Research output: Contribution to journal › Article
TY - JOUR
T1 - HIV DNA-adenovirus multiclade envelope vaccine induces gp41 antibody immunodominance in rhesus macaques
AU - Han, Qifeng
AU - Williams, Wilton B.
AU - Saunders, Kevin O.
AU - Seaton, Kelly E.
AU - Wiehe, Kevin J.
AU - Vandergrift, Nathan
AU - Von Holle, Tarra A.
AU - Trama, Ashley M.
AU - Parks, Robert J.
AU - Luo, Kan
AU - Gurley, Thaddeus C.
AU - Kepler, Thomas B.
AU - Marshall, Dawn J.
AU - Montefiori, David C.
AU - Sutherland, Laura L.
AU - Alam, Munir S.
AU - Whitesides, John F.
AU - Bowman, Cindy M.
AU - Permar, Sallie R.
AU - Graham, Barney S.
AU - Mascola, John R.
AU - Seed, Patrick C.
AU - Van Rompay, Koen K.A.
AU - Tomaras, Georgia D.
AU - Moody, M. Anthony
AU - Haynes, Barton F.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - Dominant antibody responses in vaccinees who received the HIV-1 multiclade (A, B, and C) envelope (Env) DNA/recombinant adenovirus virus type 5 (rAd5) vaccine studied in HIV-1 Vaccine Trials Network (HVTN) efficacy trial 505 (HVTN 505) targeted Env gp41 and cross-reacted with microbial antigens. In this study, we asked if the DNA/rAd5 vaccine induced a similar antibody response in rhesus macaques (RMs), which are commonly used as an animal model for human HIV-1 infections and for testing candidate HIV-1 vaccines. We also asked if gp41 immunodominance could be avoided by immunization of neonatal RMs during the early stages of microbial colonization. We found that the DNA/rAd5 vaccine elicited a higher frequency of gp41-reactive memory B cells than gp120-memory B cells in adult and neonatal RMs. Analysis of the vaccine-induced Env-reactive B cell repertoire revealed that the majority of HIV-1 Env-reactive antibodies in both adult and neonatal RMs were targeted to gp41. Interestingly, a subset of gp41- reactive antibodies isolated from RMs cross-reacted with host antigens, including autologous intestinal microbiota. Thus, gp41-containing DNA/rAd5 vaccine induced dominant gp41-microbiota cross-reactive antibodies derived from blood memory B cells in RMs as observed in the HVTN 505 vaccine efficacy trial. These data demonstrated that RMs can be used to investigate gp41 immunodominance in candidate HIV-1 vaccines. Moreover, colonization of neonatal RMs occurred within the first week of life, and immunization of neonatal RMs during this time also induced a dominant gp41-reactive antibody response.
AB - Dominant antibody responses in vaccinees who received the HIV-1 multiclade (A, B, and C) envelope (Env) DNA/recombinant adenovirus virus type 5 (rAd5) vaccine studied in HIV-1 Vaccine Trials Network (HVTN) efficacy trial 505 (HVTN 505) targeted Env gp41 and cross-reacted with microbial antigens. In this study, we asked if the DNA/rAd5 vaccine induced a similar antibody response in rhesus macaques (RMs), which are commonly used as an animal model for human HIV-1 infections and for testing candidate HIV-1 vaccines. We also asked if gp41 immunodominance could be avoided by immunization of neonatal RMs during the early stages of microbial colonization. We found that the DNA/rAd5 vaccine elicited a higher frequency of gp41-reactive memory B cells than gp120-memory B cells in adult and neonatal RMs. Analysis of the vaccine-induced Env-reactive B cell repertoire revealed that the majority of HIV-1 Env-reactive antibodies in both adult and neonatal RMs were targeted to gp41. Interestingly, a subset of gp41- reactive antibodies isolated from RMs cross-reacted with host antigens, including autologous intestinal microbiota. Thus, gp41-containing DNA/rAd5 vaccine induced dominant gp41-microbiota cross-reactive antibodies derived from blood memory B cells in RMs as observed in the HVTN 505 vaccine efficacy trial. These data demonstrated that RMs can be used to investigate gp41 immunodominance in candidate HIV-1 vaccines. Moreover, colonization of neonatal RMs occurred within the first week of life, and immunization of neonatal RMs during this time also induced a dominant gp41-reactive antibody response.
KW - Gp41
KW - HIV-1 envelope
KW - HIV-1 vaccine
KW - Microbiome
KW - Rhesus macaques
UR - http://www.scopus.com/inward/record.url?scp=85031106594&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85031106594&partnerID=8YFLogxK
U2 - 10.1128/JVI.00923-17
DO - 10.1128/JVI.00923-17
M3 - Article
C2 - 28794027
AN - SCOPUS:85031106594
VL - 91
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 21
M1 - e00923-17
ER -