Special Issue "HIV Vaccines"

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A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (31 July 2013)

Special Issue Editor

Guest Editor
Prof. Dr. Robin J. Shattock (Website)

Section of Infectious Diseases, Faculty of Medicine, Wright-Fleming Institute, St Mary's Campus, Imperial College, Norfolk Place, London W2 1PG, UK
Interests: HIV vaccines, mucosal immunity, HIV prevention/transmission, immunogen discovery, vaccine delivery strategies, replicating and non-replicating vectors

Special Issue Information

Dear Colleagues,

HIV remains a major health problem of global concern. According to estimates from the World Health Organization, over 34 million people are infected with HIV, with 7000 new infections occurring daily and 1.7 million people dying of HIV in 2011. Although current anti-retroviral therapy provides highly effective treatment, for every person starting ART two people are newly infected with 20 million more people predicted to acquire HIV by 2031, increasing potential treatment costs up to $35 billion a year. Thus successful provision of universal treatment access may be critically dependent on reducing the number of new infections. Although other biomedical interventions have an important role in reducing HIV incidence, vaccines still provide the best hope for changing the epidemic. 30 years on from the discovery of HIV, a single HIV vaccine trial has shown modest efficacy of short duration. However, great advances have been made in the discovery of broadly neutralizing antibodies together with the ontogeny of their development. This combined with recent animal model data showing profound control of viral replication by replicating vectors heralds a new era in HIV vaccine research. This special issue on “HIV Vaccines” will explore how recent science is changing the prospects for developing effective vaccines able to provide protection from acquisition and control of infection. The issue will highlight leading developments in the vaccine technology, including but not limited to, induction of neutralizing antibodies, improvements in epitope design, use of replicating and non-replicating vectors, subunit vaccines (proteins/peptides/scaffolds) and DNA. Novel mechanisms of enhancing vaccine efficacy are also welcome including research on adjuvants and biomarkers of protection against HIV. The special issue will be a mix of original research articles, and mini reviews. The main focus of this special issue is to present cutting edge research and recent developments in vaccines, which can prevent HIV acquisition and disease progression.

Prof. Dr. Robin Shattock
Guest Editor

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed Open Access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 300 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.

Keywords

  • replicating vectors and viral control
  • engaging the B cell germline
  • new molecular approaches for improving T cell potency
  • targeting functional trimers
  • mucosal immunity and HIV prevention
  • harnessing innate immunity against HIV acquisition
  • translating broadly neutralizing antibodies into effective prevention
  • prime-boost: a role for next generation DNA delivery/constructs
  • vector control: getting the best from recombinant-vector based vaccines
  • what’s needed to sustain protective antibody responses: novel adjuvant developments
  • experimental vaccine trials – the need for accelerated human immunogen discovery
  • therapeutic vaccine – can they contribute towards effective cure
  • correlates of protection: do they offer novel mechanisms for enhancing vaccine efficacy

Published Papers (8 papers)

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Research

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Open AccessArticle What Has 30 Years of HIV Vaccine Research Taught Us?
Vaccines 2013, 1(4), 513-526; doi:10.3390/vaccines1040513
Received: 21 August 2013 / Revised: 14 October 2013 / Accepted: 17 October 2013 / Published: 30 October 2013
Cited by 5 | PDF Full-text (363 KB) | HTML Full-text | XML Full-text
Abstract
When HIV was discovered and established as the cause of AIDS in 1983–1984, many people believed that a vaccine would be rapidly developed. However, 30 years have passed and we are still struggling to develop an elusive vaccine. In trying to achieve [...] Read more.
When HIV was discovered and established as the cause of AIDS in 1983–1984, many people believed that a vaccine would be rapidly developed. However, 30 years have passed and we are still struggling to develop an elusive vaccine. In trying to achieve that goal, different scientific paradigms have been explored. Although major progress has been made in understanding the scientific basis for HIV vaccine development, efficacy trials have been critical in moving the field forward. Major lessons learned are: the development of an HIV vaccine is an extremely difficult challenge; the temptation of just following the fashion should be avoided; clinical trials are critical, especially large-scale efficacy trials; HIV vaccine research will require long-term commitment; and sustainable collaborations are needed to accelerate the development of an HIV vaccine. Concrete actions must be implemented with the sense of urgency imposed by the severity of the AIDS epidemic. Full article
(This article belongs to the Special Issue HIV Vaccines)
Open AccessArticle An HIV Vaccine for South-East Asia—Opportunities and Challenges
Vaccines 2013, 1(3), 348-366; doi:10.3390/vaccines1030348
Received: 3 June 2013 / Revised: 25 July 2013 / Accepted: 5 August 2013 / Published: 14 August 2013
Cited by 2 | PDF Full-text (510 KB) | HTML Full-text | XML Full-text
Abstract
Recent advances in HIV vaccine development along with a better understanding of the immune correlates of risk have emerged from the RV144 efficacy trial conducted in Thailand. Epidemiological data suggest that CRF01_AE is still predominant in South-East Asia and is spreading in [...] Read more.
Recent advances in HIV vaccine development along with a better understanding of the immune correlates of risk have emerged from the RV144 efficacy trial conducted in Thailand. Epidemiological data suggest that CRF01_AE is still predominant in South-East Asia and is spreading in China with a growing number of circulating recombinant forms due to increasing human contact, particularly in large urban centers, tourist locations and in sites of common infrastructure. A vaccine countering CRF01_AE is a priority for the region. An Asia HIV vaccine against expanding B/E or BCE recombinant forms should be actively pursued. A major challenge that remains is the conduct of efficacy trials in heterosexual populations in this region. Men who have sex with men represent the main target population for future efficacy trials in Asia. Coupling HIV vaccines with other prevention modalities in efficacy trials might also be envisaged. These new avenues will only be made possible through the conduct of large-scale efficacy trials, interdisciplinary teams, international collaborations, and strong political and community commitments. Full article
(This article belongs to the Special Issue HIV Vaccines)

Review

Jump to: Research

Open AccessReview DNA Immunization for HIV Vaccine Development
Vaccines 2014, 2(1), 138-159; doi:10.3390/vaccines2010138
Received: 7 November 2013 / Revised: 8 February 2014 / Accepted: 10 February 2014 / Published: 25 February 2014
Cited by 1 | PDF Full-text (405 KB) | HTML Full-text | XML Full-text
Abstract
DNA vaccination has been studied in the last 20 years for HIV vaccine research. Significant experience has been accumulated in vector design, antigen optimization, delivery approaches and the use of DNA immunization as part of a prime-boost HIV vaccination strategy. Key historical [...] Read more.
DNA vaccination has been studied in the last 20 years for HIV vaccine research. Significant experience has been accumulated in vector design, antigen optimization, delivery approaches and the use of DNA immunization as part of a prime-boost HIV vaccination strategy. Key historical data and future outlook are presented. With better understanding on the potential of DNA immunization and recent progress in HIV vaccine research, it is anticipated that DNA immunization will play a more significant role in the future of HIV vaccine development. Full article
(This article belongs to the Special Issue HIV Vaccines)
Open AccessReview Advancing Toward HIV-1 Vaccine Efficacy through the Intersections of Immune Correlates
Vaccines 2014, 2(1), 15-35; doi:10.3390/vaccines2010015
Received: 29 October 2013 / Revised: 29 October 2013 / Accepted: 9 December 2013 / Published: 27 December 2013
Cited by 6 | PDF Full-text (456 KB) | HTML Full-text | XML Full-text
Abstract
Interrogating immune correlates of infection risk for efficacious and non-efficacious HIV-1 vaccine clinical trials have provided hypotheses regarding the mechanisms of induction of protective immunity to HIV-1. To date, there have been six HIV-1 vaccine efficacy trials (VAX003, Vaxgen, Inc., San Francisco, [...] Read more.
Interrogating immune correlates of infection risk for efficacious and non-efficacious HIV-1 vaccine clinical trials have provided hypotheses regarding the mechanisms of induction of protective immunity to HIV-1. To date, there have been six HIV-1 vaccine efficacy trials (VAX003, Vaxgen, Inc., San Francisco, CA, USA), VAX004 (Vaxgen, Inc.), HIV-1 Vaccine Trials Network (HVTN) 502 (Step), HVTN 503 (Phambili), RV144 (sponsored by the U.S. Military HIV Research Program, MHRP) and HVTN 505). Cellular, humoral, host genetic and virus sieve analyses of these human clinical trials each can provide information that may point to potentially protective mechanisms for vaccine-induced immunity. Critical to staying on the path toward development of an efficacious vaccine is utilizing information from previous human and non-human primate studies in concert with new discoveries of basic HIV-1 host-virus interactions. One way that past discoveries from correlate analyses can lead to novel inventions or new pathways toward vaccine efficacy is to examine the intersections where different components of the correlate analyses overlap (e.g., virus sieve analysis combined with humoral correlates) that can point to mechanistic hypotheses. Additionally, differences in durability among vaccine-induced T- and B-cell responses indicate that time post-vaccination is an important variable. Thus, understanding the nature of protective responses, the degree to which such responses have, or have not, as yet, been induced by previous vaccine trials and the design of strategies to induce durable T- and B-cell responses are critical to the development of a protective HIV-1 vaccine. Full article
(This article belongs to the Special Issue HIV Vaccines)
Figures

Open AccessReview Immune System Regulation in the Induction of Broadly Neutralizing HIV-1 Antibodies
Vaccines 2014, 2(1), 1-14; doi:10.3390/vaccines2010001
Received: 16 October 2013 / Revised: 15 November 2013 / Accepted: 9 December 2013 / Published: 19 December 2013
Cited by 4 | PDF Full-text (205 KB) | HTML Full-text | XML Full-text
Abstract
In this brief review, we discuss immune tolerance as a factor that determines the magnitude and quality of serum antibody responses to HIV-1 infection and vaccination in the context of recent work. We propose that many conserved, neutralizing epitopes of HIV-1 are [...] Read more.
In this brief review, we discuss immune tolerance as a factor that determines the magnitude and quality of serum antibody responses to HIV-1 infection and vaccination in the context of recent work. We propose that many conserved, neutralizing epitopes of HIV-1 are weakly immunogenic because they mimic host antigens. In consequence, B cells that strongly bind these determinants are removed by the physiological process of immune tolerance. This structural mimicry may represent a significant impediment to designing protective HIV-1 vaccines, but we note that several vaccine strategies may be able to mitigate this evolutionary adaptation of HIV and other microbial pathogens. Full article
(This article belongs to the Special Issue HIV Vaccines)
Open AccessReview Developing Combined HIV Vaccine Strategies for a Functional Cure
Vaccines 2013, 1(4), 481-496; doi:10.3390/vaccines1040481
Received: 5 September 2013 / Revised: 8 October 2013 / Accepted: 12 October 2013 / Published: 28 October 2013
Cited by 1 | PDF Full-text (464 KB) | HTML Full-text | XML Full-text
Abstract
Increasing numbers of HIV-infected individuals have access to potent antiretroviral drugs that control viral replication and decrease the risk of transmission. However, there is no cure for HIV and new strategies have to be developed to reach an eradication of the virus [...] Read more.
Increasing numbers of HIV-infected individuals have access to potent antiretroviral drugs that control viral replication and decrease the risk of transmission. However, there is no cure for HIV and new strategies have to be developed to reach an eradication of the virus or a natural control of viral replication in the absence of drugs (functional cure). Therapeutic vaccines against HIV have been evaluated in many trials over the last 20 years and important knowledge has been gained from these trials. However, the major obstacle to HIV eradication is the persistence of latent proviral reservoirs. Different molecules are currently tested in ART-treated subjects to reactivate these latent reservoirs. Such anti-latency agents should be combined with a vaccination regimen in order to control or eradicate reactivated latently-infected cells. New in vitro assays should also be developed to assess the success of tested therapeutic vaccines by measuring the immune-mediated killing of replication-competent HIV reservoir cells. This review provides an overview of the current strategies to combine HIV vaccines with anti-latency agents that could act as adjuvant on the vaccine-induced immune response as well as new tools to assess the efficacy of these approaches. Full article
(This article belongs to the Special Issue HIV Vaccines)
Open AccessReview Envelope Glycoprotein Trimers as HIV-1 Vaccine Immunogens
Vaccines 2013, 1(4), 497-512; doi:10.3390/vaccines1040497
Received: 6 September 2013 / Revised: 11 October 2013 / Accepted: 12 October 2013 / Published: 28 October 2013
Cited by 4 | PDF Full-text (580 KB) | HTML Full-text | XML Full-text
Abstract
The HIV-1 envelope glycoprotein spike is the target of neutralizing antibody attack, and hence represents the only relevant viral antigen for antibody-based vaccine design. Various approaches have been attempted to recapitulate Env in membrane-anchored and soluble forms, and these will be discussed [...] Read more.
The HIV-1 envelope glycoprotein spike is the target of neutralizing antibody attack, and hence represents the only relevant viral antigen for antibody-based vaccine design. Various approaches have been attempted to recapitulate Env in membrane-anchored and soluble forms, and these will be discussed here in the context of recent successes and challenges still to be overcome. Full article
(This article belongs to the Special Issue HIV Vaccines)
Open AccessReview Isotype Diversification of IgG Antibodies to HIV Gag Proteins as a Therapeutic Vaccination Strategy for HIV Infection
Vaccines 2013, 1(3), 328-342; doi:10.3390/vaccines1030328
Received: 5 June 2013 / Revised: 11 July 2013 / Accepted: 23 July 2013 / Published: 9 August 2013
PDF Full-text (447 KB) | HTML Full-text | XML Full-text
Abstract
The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of “protective” immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8 [...] Read more.
The development of vaccines to treat and prevent human immunodeficiency virus (HIV) infection has been hampered by an incomplete understanding of “protective” immune responses against HIV. Natural control of HIV-1 infection is associated with T-cell responses against HIV-1 Gag proteins, particularly CD8+ T-cell responses restricted by “protective” HLA-B alleles, but other immune responses also contribute to immune control. These immune responses appear to include IgG antibodies to HIV-1 Gag proteins, interferon-a-dependant natural killer (NK) cell responses and plasmacytoid dendritic cell (pDC) responses. Here, it is proposed that isotype diversification of IgG antibodies against HIV-1 Gag proteins, to include IgG2, as well as IgG3 and IgG1 antibodies, will broaden the function of the antibody response and facilitate accessory cell responses against HIV-1 by NK cells and pDCs. We suggest that this should be investigated as a vaccination strategy for HIV-1 infection. Full article
(This article belongs to the Special Issue HIV Vaccines)

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