scholarly journals Scarcity or Absence of Humoral Immune Responses in the Plasma and Cervicovaginal Lavage Fluids of Heavily HIV-1-Exposed But Persistently Seronegative Women

2011 ◽  
Vol 27 (5) ◽  
pp. 469-486 ◽  
Author(s):  
Jiri Mestecky ◽  
Peter F. Wright ◽  
Lucia Lopalco ◽  
Herman F. Staats ◽  
Pamela A. Kozlowski ◽  
...  
2005 ◽  
Vol 79 (8) ◽  
pp. 4927-4935 ◽  
Author(s):  
B. Poon ◽  
J. T. Safrit ◽  
H. McClure ◽  
C. Kitchen ◽  
J. F. Hsu ◽  
...  

ABSTRACT The lack of success of subunit human immunodeficiency virus type 1 (HIV-1) vaccines to date suggests that multiple components or a complex virion structure may be required. We previously demonstrated retention of the major conformational epitopes of HIV-1 envelope following thermal treatment of virions. Moreover, antibody binding to some of these epitopes was significantly enhanced following thermal treatment. These included the neutralizing epitopes identified by monoclonal antibodies 1b12, 2G12, and 17b, some of which have been postulated to be partially occluded or cryptic in native virions. Based upon this finding, we hypothesized that a killed HIV vaccine could be derived to elicit protective humoral immune responses. Shedding of HIV-1 envelope has been described for some strains of HIV-1 and has been cited as one of the major impediments to developing an inactivated HIV-1 vaccine. In the present study, we demonstrate that treatment of virions with low-dose formaldehyde prior to thermal inactivation retains the association of viral envelope with virions. Moreover, mice and nonhuman primates vaccinated with formaldehyde-treated, thermally inactivated virions produce antibodies capable of neutralizing heterologous strains of HIV in peripheral blood mononuclear cell-, MAGI cell-, and U87-based infectivity assays. These data indicate that it is possible to create an immunogen by using formaldehyde-treated, thermally inactivated HIV-1 virions to induce neutralizing antibodies. These findings have broad implications for vaccine development.


2009 ◽  
Vol 5 (5) ◽  
pp. e1000445 ◽  
Author(s):  
Barna Dey ◽  
Krisha Svehla ◽  
Ling Xu ◽  
Dianne Wycuff ◽  
Tongqing Zhou ◽  
...  

2016 ◽  
Vol 110 (2) ◽  
pp. 39-47 ◽  
Author(s):  
Sima Velashjerdi Farahani ◽  
Mohammad Reza Aghasadeghi ◽  
Arash Memarnejadian ◽  
Sobhan Faezi ◽  
Zahra Shahosseini ◽  
...  

2006 ◽  
Vol 112 (2) ◽  
pp. 175-185 ◽  
Author(s):  
Yasemin Ataman-Önal ◽  
Séverine Munier ◽  
Arnaud Ganée ◽  
Céline Terrat ◽  
Pierre-Yves Durand ◽  
...  

2015 ◽  
Vol 89 (16) ◽  
pp. 8525-8539 ◽  
Author(s):  
Juan García-Arriaza ◽  
Beatriz Perdiguero ◽  
Jonathan Heeney ◽  
Michael Seaman ◽  
David C. Montefiori ◽  
...  

ABSTRACTWe compared the HIV-1-specific cellular and humoral immune responses elicited in rhesus macaques immunized with two poxvirus vectors (NYVAC and ALVAC) expressing the same HIV-1 antigens from clade C, Env gp140 as a trimeric cell-released protein and a Gag-Pol-Nef polyprotein as Gag-induced virus-like particles (VLPs) (referred to as NYVAC-C and ALVAC-C). The immunization protocol consisted of two doses of the corresponding poxvirus vector plus two doses of a combination of the poxvirus vector and a purified HIV-1 gp120 protein from clade C. This immunogenicity profile was also compared to that elicited by vaccine regimens consisting of two doses of the ALVAC vector expressing HIV-1 antigens from clades B/E (ALVAC-vCP1521) plus two doses of a combination of ALVAC-vCP1521 and HIV-1 gp120 protein from clades B/E (similar to the RV144 trial regimen) or clade C. The results showed that immunization of macaques with NYVAC-C stimulated at different times more potent HIV-1-specific CD4+T-cell responses and induced a trend toward higher-magnitude HIV-1-specific CD8+T-cell immune responses than did ALVAC-C. Furthermore, NYVAC-C induced a trend toward higher levels of binding IgG antibodies against clade C HIV-1 gp140, gp120, or murine leukemia virus (MuLV) gp70-scaffolded V1/V2 and toward best cross-clade-binding IgG responses against HIV-1 gp140 from clades A, B, and group M consensus, than did ALVAC-C. Of the linear binding IgG responses, most were directed against the V3 loop in all immunization groups. Additionally, NYVAC-C and ALVAC-C also induced similar levels of HIV-1-neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC) responses. Interestingly, binding IgA antibody levels against HIV-1 gp120 or MuLV gp70-scaffolded V1/V2 were absent or very low in all immunization groups. Overall, these results provide a comprehensive survey of the immunogenicity of NYVAC versus ALVAC expressing HIV-1 antigens in nonhuman primates and indicate that NYVAC may represent an alternative candidate to ALVAC in the development of a future HIV-1 vaccine.IMPORTANCEThe finding of a safe and effective HIV/AIDS vaccine immunogen is one of the main research priorities. Here, we generated two poxvirus-based HIV vaccine candidates (NYVAC and ALVAC vectors) expressing the same clade C HIV-1 antigens in separate vectors, and we analyzed in nonhuman primates their immunogenicity profiles. The results showed that immunization with NYVAC-C induced a trend toward higher HIV-1-specific cellular and humoral immune responses than did ALVAC-C, indicating that this new NYVAC vector could be a novel optimized HIV/AIDS vaccine candidate for human clinical trials.


Vaccine ◽  
2015 ◽  
Vol 33 (36) ◽  
pp. 4430-4436 ◽  
Author(s):  
Lumin Zhang ◽  
Zihai Li ◽  
Zhuang Wan ◽  
Andrew Kilby ◽  
J. Michael Kilby ◽  
...  

2004 ◽  
Vol 78 (13) ◽  
pp. 7061-7068 ◽  
Author(s):  
Wendy Fitzgerald ◽  
Andrew W. Sylwester ◽  
Jean-Charles Grivel ◽  
Jeffrey D. Lifson ◽  
Leonid B. Margolis

ABSTRACT Ex vivo human immunodeficiency virus type 1 (HIV-1) infection of human lymphoid tissue recapitulates some aspects of in vivo HIV-1 infection, including a severe depletion of CD4+ T cells and suppression of humoral immune responses to recall antigens or to polyclonal stimuli. These effects are induced by infection with X4 HIV-1 variants, whereas infection with R5 variants results in only mild depletion of CD4+ T cells and no suppression of immune responses. To study the mechanisms of suppression of immune responses in this ex vivo system, we used aldrithiol-2 (AT-2)-inactivated virions that have functional envelope glycoproteins but are not infectious and do not deplete CD4+ T cells in human lymphoid tissues ex vivo. Nevertheless, AT-2-inactivated X4 (but not R5) HIV-1 virions, even with only a brief exposure, inhibit antibody responses in human lymphoid tissue ex vivo, similarly to infectious virus. This phenomenon is mediated by soluble immunosuppressive factor(s) secreted by tissue exposed to virus.


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