AIDS Vaccine

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (30 December 2009) | Viewed by 133306

Special Issue Editor

1. Institute of Molecular and Medical Virology, School of Medicine, Jinan University, 601 Huangpu Ave. West, Guangzhou 510632, China
2. Department of Medicine, Duke University Medical Center, 303 Research Dr., DUMC 102359, Durham, NC 27710, USA
Interests: HIV; genetic variation and evolution; vaccine; drug resistance
Special Issues, Collections and Topics in MDPI journals

Published Papers (10 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

579 KiB  
Article
The Evolution of HIV-1 Diversity in Rural Cameroon and its Implications in Vaccine Design and Trials
by Rebecca Powell, Denis Barengolts, Luzia Mayr and Phillipe Nyambi
Viruses 2010, 2(2), 639-654; https://doi.org/10.3390/v2020639 - 12 Feb 2010
Cited by 9 | Viewed by 9194
Abstract
West-Central Africa is an epicenter of the HIV pandemic; endemic to Cameroon are HIV-1 viruses belonging to all (sub)subtypes and numerous Circulating Recombinant Forms (CRFs). The rural villages of Cameroon harbor many strains of HIV-1, though these areas are not as well monitored [...] Read more.
West-Central Africa is an epicenter of the HIV pandemic; endemic to Cameroon are HIV-1 viruses belonging to all (sub)subtypes and numerous Circulating Recombinant Forms (CRFs). The rural villages of Cameroon harbor many strains of HIV-1, though these areas are not as well monitored as the urban centers. In the present study, 82 specimens obtained in 2000 and 2001 from subjects living in the rural villages of the South and West Regions of Cameroon were subtyped in gag, pol, and env and compared to 90 specimens obtained in 2006–2008 in the same regions, in order to analyze HIV-1 evolution in these rural areas. It was found that in the South Region, the proportion of unique recombinant forms (URFs) remained constant (~40%), while the amount of URFs containing fragments of a CRF increased by 25%. (Sub)subtypes A1, F2, H, and K, and CRF09_cpx, identified in 2000 and 2001, were replaced by CRFs 01_AE, 13_cpx, 14_BG, and 18_cpx in 2006–2008. In the West Region, (sub)subtypes A2, C, G, and H, and CRFs 01_AE and 09_cpx, identified in 2000–2001, were replaced by sub-subtype A1 and CRFs 25_cpx and 37_cpx in 2006–2008. The proportion of URFs in the West Region dropped significantly over the time period by 43%. In both Regions, the proportion of CRF02_AG increased at all loci. These findings demonstrate that the evolution of HIV-1 is distinct for each endemic region, and suggests that the proportion of URFs containing CRF fragments is increasing as the genetic identity of the virus continues to shift dramatically. This highlights the concern that subtype-specific vaccines may not be relevant in Cameroon, and that the distribution of viral diversity in these regions of Cameroon must be carefully monitored. Full article
(This article belongs to the Special Issue AIDS Vaccine)
Show Figures

180 KiB  
Article
Cross-Reactive Human IgM-Derived Monoclonal Antibodies that Bind to HIV-1 Envelope Glycoproteins
by Weizao Chen, Zhongyu Zhu, Huaxin Liao, Gerald V. Quinnan, Jr., Christopher C. Broder, Barton F. Haynes and Dimiter S. Dimitrov
Viruses 2010, 2(2), 547-565; https://doi.org/10.3390/v2020547 - 04 Feb 2010
Cited by 13 | Viewed by 10738
Abstract
Elicitation of antibodies with potent and broad neutralizing activity against HIV by immunization remains a challenge. Several monoclonal antibodies (mAbs) isolated from humans with HIV-1 infection exhibit such activity but vaccine immunogens based on structures containing their epitopes have not been successful for [...] Read more.
Elicitation of antibodies with potent and broad neutralizing activity against HIV by immunization remains a challenge. Several monoclonal antibodies (mAbs) isolated from humans with HIV-1 infection exhibit such activity but vaccine immunogens based on structures containing their epitopes have not been successful for their elicitation. All known broadly neutralizing mAbs (bnmAbs) are immunoglobulin (Ig) Gs (IgGs) and highly somatically hypermutated which could impede their elicitation. Ig Ms (IgMs) are on average significantly less divergent from germline antibodies and are relevant for the development of vaccine immunogens but are underexplored compared to IgGs. Here we describe the identification and characterization of several human IgM-derived mAbs against HIV-1 which were selected from a large phage-displayed naive human antibody library constructed from blood, lymph nodes and spleens of 59 healthy donors. These antibodies bound with high affinity to recombinant envelope glycoproteins (gp140s, Envs) of HIV-1 isolates from different clades. They enhanced or did not neutralize infection by some of the HIV-1 primary isolates using CCR5 as a coreceptor but neutralized all CXCR4 isolates tested although weakly. One of these antibodies with relatively low degree of somatic hypermutation was more extensively characterized. It bound to a highly conserved region partially overlapping with the coreceptor binding site and close to but not overlapping with the CD4 binding site. These results suggest the existence of conserved structures that could direct the immune response to non-neutralizing or even enhancing antibodies which may represent a strategy used by the virus to escape neutralizing immune responses. Further studies will show whether such a strategy plays a role in HIV infection of humans, how important that role could be, and what the mechanisms of infection enhancement are. The newly identified mAbs could be used as reagents to further characterize conserved non-neutralizing, weakly neutralizing or enhancing epitopes and modify or remove them from candidate vaccine immunogens. Full article
(This article belongs to the Special Issue AIDS Vaccine)
Show Figures

Figure 1

35 KiB  
Communication
Preliminary Report on HIV-1 Vaccine Preparedness in Nigeria: Advantages of Recruiting University Students
by Abigail Edubio, Simon Agwale, Marc Bulterys, Dadik Jelpe, John Idoko, Chris Isichei, Ruth Guyit and Alash’le Abimiku
Viruses 2010, 2(1), 73-77; https://doi.org/10.3390/v2010073 - 11 Jan 2010
Cited by 2 | Viewed by 10828
Abstract
The national HIV seroprevalence in Nigeria has risen steeply from about 3% in 1993 to 5-8% in 2001 and now stands at 4.4%. HIV epidemic continues to be a serious threat to the most populous country in Africa with a population of 140 [...] Read more.
The national HIV seroprevalence in Nigeria has risen steeply from about 3% in 1993 to 5-8% in 2001 and now stands at 4.4%. HIV epidemic continues to be a serious threat to the most populous country in Africa with a population of 140 million, with limited use of antiviral drugs that is taken for life since it only suppresses the virus without completely eliminating the virus or leading to cure. Only a change in social behavior and an affordable vaccine can halt the epidemic in Africa. We report here results of a pilot study on the recruitment strategies, sociodemographic aspects and HIV risk behavior of a cohort of normal volunteers recruited at the University of Jos, Nigeria. Our study recorded a high degree of interest and zeal to participate in HIV vaccine studies by volunteers, and demonstrated the superiority of snowballing over invitation by mail, as a recruitment strategy. A cohort of university students may be particularly suitable for conducting HIV vaccine trials because of the assurance of prospective follow-up for up to four years (time to graduation), and a good understanding of the risks and benefits of participation as outlined in the informed consent. We had 100% retention during a follow-up period of two years. Most importantly, the cohort reflected a relatively low HIV seroprevalence, which gives preventive programs the potential to blunt or halt the epidemic. Full article
(This article belongs to the Special Issue AIDS Vaccine)
294 KiB  
Article
HIV-1 Subtype C Phylodynamics in the Global Epidemic
by Vlad Novitsky, Rui Wang, Stephen Lagakos and Max Essex
Viruses 2010, 2(1), 33-54; https://doi.org/10.3390/v2010033 - 07 Jan 2010
Cited by 23 | Viewed by 14554
Abstract
The diversity of HIV-1 and its propensity to generate escape mutants present fundamental challenges to control efforts, including HIV vaccine design. Intra-host diversification of HIV is determined by immune responses elicited by an HIV-infected individual over the course of the infection. Complex and [...] Read more.
The diversity of HIV-1 and its propensity to generate escape mutants present fundamental challenges to control efforts, including HIV vaccine design. Intra-host diversification of HIV is determined by immune responses elicited by an HIV-infected individual over the course of the infection. Complex and dynamic patterns of transmission of HIV lead to an even more complex population viral diversity over time, thus presenting enormous challenges to vaccine development. To address inter-patient viral evolution over time, a set of 653 unique HIV-1 subtype C gag sequences were retrieved from the LANL HIV Database, grouped by sampling year as <2000, 2000, 2001–2002, 2003, and 2004–2006, and analyzed for the site-specific frequency of translated amino acid residues. Phylogenetic analysis revealed that a total of 289 out of 653 (44.3%) analyzed sequences were found within 16 clusters defined by aLRT of more than 0.90. Median (IQR) inter-sample diversity of analyzed gag sequences was 8.7% (7.7%; 9.8%). Despite the heterogeneous origins of analyzed sequences, the gamut and frequency of amino acid residues in wild-type Gag were remarkably stable over the last decade of the HIV-1 subtype C epidemic. The vast majority of amino acid residues demonstrated minor frequency fluctuation over time, consistent with the conservative nature of the HIV-1 Gag protein. Only 4.0% (20 out of 500; HXB2 numbering) amino acid residues across Gag displayed both statistically significant (p<0.05 by both a trend test and heterogeneity test) changes in amino acid frequency over time as well as a range of at least 10% in the frequency of the major amino acid. A total of 59.2% of amino acid residues with changing frequency of 10%+ were found within previously identified CTL epitopes. The time of the most recent common ancestor of the HIV-1 subtype C was dated to around 1950 (95% HPD from 1928 to 1962). This study provides evidence for the overall stability of HIV-1 subtype C Gag among viruses circulating in the epidemic over the last decade. However selected sites across HIV-1C Gag with changing amino acid frequency are likely to be under selection pressure at the population level. Full article
(This article belongs to the Special Issue AIDS Vaccine)
Show Figures

Figure 1

580 KiB  
Article
Protection against Mucosal SHIV Challenge by Peptide and Helper-Dependent Adenovirus Vaccines
by Eric A. Weaver, Pramod N. Nehete, Bharti P. Nehete, Stephanie J. Buchl, Donna Palmer, David C. Montefiori, Philip Ng, K. Jagannadha Sastry and Michael A. Barry
Viruses 2009, 1(3), 920-938; https://doi.org/10.3390/v1030920 - 10 Nov 2009
Cited by 29 | Viewed by 11955
Abstract
Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helperdependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. [...] Read more.
Groups of rhesus macaques that had previously been immunized with HIV-1 envelope (env) peptides and first generation adenovirus serotype 5 (FG-Ad5) vaccines expressing the same peptides were immunized intramuscularly three times with helperdependent adenovirus (HD-Ad) vaccines expressing only the HIV-1 envelope from JRFL. No gag, pol, or other SHIV genes were used for vaccination. One group of the FG-Ad5-immune animals was immunized three times with HD-Ad5 expressing env. One group was immunized by serotype-switching with HD-Ad6, HD-Ad1, and HD-Ad2 expressing env. Previous work demonstrated that serum antibody levels against env were significantly higher in the serotype-switched group than in the HD-Ad5 group. In this study, neutralizing antibody and T cell responses were compared between the groups before and after rectal challenge with CCR5-tropic SHIV-SF162P3. When serum samples were assayed for neutralizing antibodies, only weak activity was observed. T cell responses against env epitopes were higher in the serotype-switched group. When these animals were challenged rectally with SHIV-SF162P3, both the Ad5 and serotype-switch groups significantly reduced peak viral loads 2 to 10-fold 2 weeks after infection. Peak viral loads were significantly lower for the serotype-switched group as compared to the HD-Ad5-immunized group. Viral loads declined over 18 weeks after infection with some animals viremia reducing nearly 4 logs from the peak. These data demonstrate significant mucosal vaccine effects after immunization with only env antigens. These data also demonstrate HD-Ad vectors are a robust platform for vaccination. Full article
(This article belongs to the Special Issue AIDS Vaccine)
Show Figures

657 KiB  
Article
Maturation Pathways of Cross-Reactive HIV-1 Neutralizing Antibodies
by Xiaodong Xiao, Weizao Chen, Yang Feng and Dimiter S. Dimitrov
Viruses 2009, 1(3), 802-817; https://doi.org/10.3390/v1030802 - 06 Nov 2009
Cited by 53 | Viewed by 13325
Abstract
Several human monoclonal antibodies (hmAbs) and antibody fragments, including the best characterized in terms of structure-function b12 and Fab X5, exhibit relatively potent and broad HIV-1 neutralizing activity. However, the elicitation of b12 or b12-like antibodies in vivo by vaccine immunogens based on [...] Read more.
Several human monoclonal antibodies (hmAbs) and antibody fragments, including the best characterized in terms of structure-function b12 and Fab X5, exhibit relatively potent and broad HIV-1 neutralizing activity. However, the elicitation of b12 or b12-like antibodies in vivo by vaccine immunogens based on the HIV-1 envelope glycoprotein (Env) has not been successful. B12 is highly divergent from the closest corresponding germline antibody while X5 is less divergent. We have hypothesized that the relatively high degree of specific somatic hypermutations may preclude binding of the HIV-1 envelope glycoprotein (Env) to closest germline antibodies, and that identifying antibodies that are intermediates in the pathways to maturation could help design novel vaccine immunogens to guide the immune system for their enhanced elicitation. In support of this hypothesis we have previously found that a germline-like b12 (monovalent and bivalent scFv as an Fc fusion protein or IgG) lacks measurable binding to an Env as measured by ELISA with a sensitivity in the μM range [1]; here we present evidence confirming and expanding these findings for a panel of Envs. In contrast, a germline-like scFv X5 bound Env with high (nM) affinity. To begin to explore the maturation pathways of these antibodies we identified several possible b12 intermediate antibodies and tested their neutralizing activity. These intermediate antibodies neutralized only some HIV-1 isolates and with relatively weak potency. In contrast, germline-like scFv X5 neutralized a subset of the tested HIV-1 isolates with comparable efficiencies to that of the mature X5. These results could help explain the relatively high immunogenicity of the coreceptor binding site on gp120 and the abundance of CD4-induced (CD4i) antibodies in HIV-1-infected patients (X5 is a CD4i antibody) as well as the maturation pathway of X5. They also can help identify antigens that can bind specifically to b12 germline and intermediate antibodies that together with Envs could be used as a conceptually novel type of candidate vaccines. Such candidate vaccines based on two or more immunogens could help guiding the immune system through complex maturation pathways for elicitation of antibodies that are similar or identical to antibodies with known properties. Full article
(This article belongs to the Special Issue AIDS Vaccine)
Show Figures

Figure 1

Review

Jump to: Research

834 KiB  
Review
CCR5: From Natural Resistance to a New Anti-HIV Strategy
by Lucia Lopalco
Viruses 2010, 2(2), 574-600; https://doi.org/10.3390/v2020574 - 05 Feb 2010
Cited by 95 | Viewed by 25293
Abstract
The C-C chemokine receptor type 5 (CCR5) is a key player in HIV infection due to its major involvement in the infection process. Investigations into the role of the CCR5 coreceptor first focused on its binding to the virus and the molecular mechanisms [...] Read more.
The C-C chemokine receptor type 5 (CCR5) is a key player in HIV infection due to its major involvement in the infection process. Investigations into the role of the CCR5 coreceptor first focused on its binding to the virus and the molecular mechanisms leading to the entry and spread of HIV. The identification of naturally occurring CCR5 mutations has allowed scientists to address the CCR5 molecule as a promising target to prevent or limit HIV infection in vivo. Naturally occurring CCR5-specific antibodies have been found in exposed but uninfected people, and in a subset of HIV seropositive people who show long-term control of the infection. This suggests that natural autoimmunity to the CCR5 coreceptor exists and may play a role in HIV control. Such natural immunity has prompted strategies aimed at achieving anti-HIV humoral responses through CCR5 targeting, which will be described here. Full article
(This article belongs to the Special Issue AIDS Vaccine)
Show Figures

Figure 1

216 KiB  
Review
Heterologous Prime-Boost HIV-1 Vaccination Regimens in Pre-Clinical and Clinical Trials
by Scott A. Brown, Sherri L. Surman, Robert Sealy, Bart G. Jones, Karen S. Slobod, Kristen Branum, Timothy D. Lockey, Nanna Howlett, Pamela Freiden, Patricia Flynn and Julia L. Hurwitz
Viruses 2010, 2(2), 435-467; https://doi.org/10.3390/v2020435 - 01 Feb 2010
Cited by 35 | Viewed by 13752
Abstract
Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat [...] Read more.
Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat encouraging results in an advanced clinical efficacy trial. A modified intent-to-treat analysis of trial results showed that infection was approximately 30% lower in the vaccine group compared to the placebo group. The vaccine was administered using a heterologous prime-boost regimen in which both target antigens and delivery vehicles were changed during the course of inoculations. Here we examine the complexity of heterologous prime-boost immunizations. We show that the use of different delivery vehicles in prime and boost inoculations can help to avert the inhibitory effects caused by vector-specific immune responses. We also show that the introduction of new antigens into boost inoculations can be advantageous, demonstrating that the effect of ‘original antigenic sin’ is not absolute. Pre-clinical and clinical studies are reviewed, including our own work with a three-vector vaccination regimen using recombinant DNA, virus (Sendai virus or vaccinia virus) and protein. Promising preliminary results suggest that the heterologous prime-boost strategy may possibly provide a foundation for the future prevention of HIV-1 infections in humans. Full article
(This article belongs to the Special Issue AIDS Vaccine)
Show Figures

Figure 1

107 KiB  
Review
The Development of an AIDS Mucosal Vaccine
by Xian Tang and Zhiwei Chen
Viruses 2010, 2(1), 283-297; https://doi.org/10.3390/v2010283 - 22 Jan 2010
Cited by 5 | Viewed by 11807
Abstract
It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible [...] Read more.
It is well known that mucosal tissues contain the largest surface area of the human body and are the front line of natural host defense against various pathogens. In fact, more than 80% of infectious disease pathogens probably gain entry into the susceptible human hosts through open mucosal surfaces. Human immunodeficiency virus type one (HIV-1), a mainly sexually transmitted virus, also primarily targets the vaginal and gastrointestinal mucosa as entry sites for viral transmission, seeding, replication and amplification. Since HIV-1 establishes its early replication in vaginal or rectal mucosal tissues, the induction of sufficient mucosal immunity at the initial site of HIV-1 transmission becomes essential for a protective vaccine. However, despite the fact that current conventional vaccine strategies have remained unsuccessful in preventing HIV-1 infection, sufficient financial support and resources have yet to be given to develop a vaccine able to elicit protective mucosal immunity against sexual transmissions. Interestingly, Chinese ancestors invented variolation through intranasal administration about one thousand years ago, which led to the discovery of a successful smallpox vaccine and the final eradication of the disease. It is the hope for all mankind that the development of a mucosal AIDS vaccine will ultimately help control the AIDS pandemic. In order to discover an effective mucosal AIDS vaccine, it is necessary to have a deep understanding of mucosal immunology and to test various mucosal vaccination strategies. Full article
(This article belongs to the Special Issue AIDS Vaccine)
295 KiB  
Review
Antibody-Mediated Fcγ Receptor-Based Mechanisms of HIV Inhibition: Recent Findings and New Vaccination Strategies
by Vincent Holl, Maryse Peressin and Christiane Moog
Viruses 2009, 1(3), 1265-1294; https://doi.org/10.3390/v1031265 - 15 Dec 2009
Cited by 21 | Viewed by 11223
Abstract
The HIV/AIDS pandemic is one of the most devastating pandemics worldwide. Today, the major route of infection by HIV is sexual transmission. One of the most promising strategies for vaccination against HIV sexual infection is the development of a mucosal vaccine, which should [...] Read more.
The HIV/AIDS pandemic is one of the most devastating pandemics worldwide. Today, the major route of infection by HIV is sexual transmission. One of the most promising strategies for vaccination against HIV sexual infection is the development of a mucosal vaccine, which should be able to induce strong local and systemic protective immunity. It is believed that both humoral and cellular immune responses are needed for inducing a sterilizing protection against HIV. Recently, passive administration of monoclonal neutralizing antibodies in macaques infected by vaginal challenge demonstrated a crucial role of FcγRs in the protection afforded by these antibodies. This questioned about the role of innate and adaptive immune functions, including ADCC, ADCVI, phagocytosis of opsonized HIV particles and the production of inflammatory cytokines and chemokines, in the mechanism of HIV inhibition in vivo. Other monoclonal antibodies - non-neutralizing inhibitory antibodies - which recognize immunogenic epitopes, have been shown to display potent FcγRs-dependent inhibition of HIV replication in vitro. The potential role of these antibodies in protection against sexual transmission of HIV and their biological relevance for the development of an HIV vaccine therefore need to be determined. This review highlights the potential role of FcγRsmediated innate and adaptive immune functions in the mechanism of HIV protection. Full article
(This article belongs to the Special Issue AIDS Vaccine)
Show Figures

Figure 1

Back to TopTop