scholarly journals AIDSVAX protein boost improves breadth and magnitude of vaccine-induced HIV-1 envelope-specific responses after a 7-year rest period

Vaccine ◽  
2021 ◽  
Author(s):  
Yunda Huang ◽  
Kelly E. Seaton ◽  
Martin Casapia ◽  
Laura Polakowski ◽  
Stephen C. De Rosa ◽  
...  
Keyword(s):  
2014 ◽  
Vol 10 (7) ◽  
pp. 1985-1992 ◽  
Author(s):  
Kristin Hollister ◽  
Yuxin Chen ◽  
Shixia Wang ◽  
Hao Wu ◽  
Arpita Mondal ◽  
...  

2012 ◽  
Vol 8 (11) ◽  
pp. 1630-1637 ◽  
Author(s):  
Mingshun Zhang ◽  
Lu Zhang ◽  
Chunhua Zhang ◽  
Kunxue Hong ◽  
Yiming Shao ◽  
...  

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Amin Hadi ◽  
Abbas Rastgoo ◽  
Maryam Eskandarian ◽  
Nooshin Haghighipour ◽  
Azam Bolhassani

An effective therapeutic vaccine to eradicate HIV-1 infection does not exist yet. Among different vaccination strategies, cell-based vaccines could achieve in clinical trials. Cell viability and low nucleic acid expression are the problems related to dendritic cells (DCs) and mesenchymal stem cells (MSCs), which are transfected with plasmid DNA. Thus, novel in vitro strategies are needed to improve DNA transfection into these cells. The recent study assessed immune responses generated by MSCs and DCs, which were derived from mouse bone marrow and modified with Nef antigen using novel methods in mice. For this purpose, an excellent gene transfection approach by mechanical methods was used. Our data revealed that the transfection efficacy of Nef DNA into the immature MSCs and DCs was improved by the combination of chemical and mechanical (causing equiaxial cyclic stretch) approaches. Also, chemical transfection performed two times with 48-hour intervals further increased gene expression in both cells. The groups immunized with Nef DC prime/rNef protein boost and then Nef MSC prime/rNef protein boost were able to stimulate high levels of IFN-γ, IgG2b, IgG2a, and Granzyme B directed toward Th1 responses in mice. Furthermore, the mesenchymal or dendritic cell-based immunizations were more effective compared to protein immunization for enhancement of the Nef-specific T-cell responses in mice. Hence, the use of chemical reagent and mechanical loading simultaneously can be an excellent method in delivering cargoes into DCs and MSCs. Moreover, DC- and MSC-based immunizations can be considered as promising approaches for protection against HIV-1 infections.


2016 ◽  
Vol 90 (22) ◽  
pp. 10362-10378 ◽  
Author(s):  
Matthew R. Costa ◽  
Justin Pollara ◽  
Regina Whitney Edwards ◽  
Michael S. Seaman ◽  
Miroslaw K. Gorny ◽  
...  

ABSTRACTHIV-1 is able to elicit broadly potent neutralizing antibodies in a very small subset of individuals only after several years of infection, and therefore, vaccines that elicit these types of antibodies have been difficult to design. The RV144 trial showed that moderate protection is possible and that this protection may correlate with antibody-dependent cellular cytotoxicity (ADCC) activity. Our previous studies demonstrated that in an HIV vaccine phase I trial, the DP6-001 trial, a polyvalent Env DNA prime-protein boost formulation could elicit potent and broadly reactive, gp120-specific antibodies with positive neutralization activities. Here we report on the production and analysis of HIV-1 Env-specific human monoclonal antibodies (hMAbs) isolated from vaccinees in the DP6-001 trial. For this initial report, 13 hMAbs from four vaccinees in the DP6-001 trial showed broad binding to gp120 proteins of diverse subtypes both autologous and heterologous to vaccine immunogens. Equally cross-reactive Fc receptor-mediated functional activities, including ADCC and antibody-dependent cellular phagocytosis (ADCP) activities, were present with both immune sera and isolated MAbs, confirming the induction of nonneutralizing functional hMAbs by the DNA prime-protein boost vaccination. Elicitation of broadly reactive hMAbs by vaccination in healthy human volunteers confirms the value of the polyvalent formulation in this HIV vaccine design.IMPORTANCEThe roles of Fc receptor-mediated protective antibody responses are gaining more attention due to their potential contribution to the low-level protection against HIV-1 infection that they provided in the RV144 trial. At the same time, information about hMabs from other human HIV vaccine studies is very limited. In the current study, both immune sera and monoclonal antibodies from vaccinated humans showed not only high-level ADCC and ADCP activities but also cross-subtype ADCC and ADCP activities when a polyvalent DNA prime-protein boost vaccine formulation was used.


PLoS ONE ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. e0194266 ◽  
Author(s):  
Yingxia Wen ◽  
Hung V. Trinh ◽  
Christine E. Linton ◽  
Chiara Tani ◽  
Nathalie Norais ◽  
...  
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PLoS ONE ◽  
2016 ◽  
Vol 11 (7) ◽  
pp. e0157391 ◽  
Author(s):  
Carlo Zambonelli ◽  
Antu K. Dey ◽  
Susan Hilt ◽  
Samuel Stephenson ◽  
Eden P. Go ◽  
...  

Vaccine ◽  
2008 ◽  
Vol 26 (31) ◽  
pp. 3947-3957 ◽  
Author(s):  
Shixia Wang ◽  
Jeffrey S. Kennedy ◽  
Kim West ◽  
David C. Montefiori ◽  
Scott Coley ◽  
...  

2007 ◽  
Vol 81 (8) ◽  
pp. 4272-4285 ◽  
Author(s):  
Mansun Law ◽  
Rosa M. F. Cardoso ◽  
Ian A. Wilson ◽  
Dennis R. Burton

ABSTRACT The membrane-proximal external region (MPER) of human immunodeficiency virus type 1 (HIV-1) gp41 is a target of broadly neutralizing monoclonal antibodies (MAbs) 2F5, 4E10, and Z13. Here we engrafted the MPER into the V1/2 region of HIV-1 gp120 to investigate the ability of the engineered antigens to elicit virus-neutralizing antibodies (NAbs). To promote the correct folding and presentation of the helical 4E10 epitope, we flanked the epitope with helical domains and manipulated the helix by sequential deletion of residues preceding the epitope. Binding of the recombinant proteins to MAb 4E10 increased four- to fivefold with the deletion of one or two residues, but it returned to the wild-type level when three residues were deleted, suggesting rotation of the 4E10 epitope along the helix. Immunization of mice and rabbits by electroporation-mediated DNA priming and protein boosting with these constructs elicited high levels of gp120-specific antibodies. A consistent NAb response against the neutralization-resistant, homologous JR-FL virus was detected in rabbits but not in mice. Analysis of the neutralizing activity revealed that the NAbs do not target the MPER or the V1, V2, or V3 region. Through this study, we learned the following. (i) The 4E10 epitope can be manipulated using a “rotate-the-helix” strategy that alters the helix register. However, presentation of this epitope in the immunogenic V1/2 region did not render it immunogenic in mice or rabbits. (ii) DNA vaccination with monomeric gp120-based antigens can elicit a consistent NAb response against the homologous neutralization-resistant virus by targeting epitopes outside the V1, V2, and V3 regions.


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