Accelerating the development of a safe and effective HIV vaccine: HIV vaccine case study for the Decade of Vaccines

Koff, Wayne C.; Russell, Nina D.; Walport, Mark J.; Feinberg, Mark B.; Shiver, John W.; Karim, Salim Safurdeen. Abdool; Walker, Bruce D.; McGlynn, Margaret G.; Nweneka, Chidi Victor; Nabel, Gary J.

doi:10.1016/j.vaccine.2012.10.115

Cited by 27 publications

(12 citation statements)

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“…It is estimated that about 780,000 people are currently living with HIV/AIDS in China, with 434,000 cases reported to the National Health and Family Planning Commission of China until October 2013 (http://www.gov.cn/jrzg/2013-12/01/content_2539529.htm). The strategies for controlling the global HIV epidemic include escalating the usage of condoms, developing vaccine and vaginal/rectal microbicides and implementing treatment as prevention [2], [3]. As an effective vaccine remains as the most cost-effective approach and less depends on human behavior for success [2], thus, the development of an effective and safe vaccine for prevention of AIDS remains as a global public health priority and the greatest opportunity to eventually end the AIDS pandemic [2], [4], [5].…”

Section: Introductionmentioning

confidence: 99%

“…The strategies for controlling the global HIV epidemic include escalating the usage of condoms, developing vaccine and vaginal/rectal microbicides and implementing treatment as prevention [2], [3]. As an effective vaccine remains as the most cost-effective approach and less depends on human behavior for success [2], thus, the development of an effective and safe vaccine for prevention of AIDS remains as a global public health priority and the greatest opportunity to eventually end the AIDS pandemic [2], [4], [5]. However, after thirty years of research, it remains elusive whether a protective vaccine will be developed, despite strong optimism from previous trials [6], [7].…”

Section: Introductionmentioning

confidence: 99%

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Willingness to Participate in HIV Therapeutic Vaccine Trials among HIV-Infected Patients on ART in China

et al. 2014

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BackgroundMore and more HIV therapeutic vaccines will enter clinical trials; however, little is known about the willingness to participate (WTP) in HIV therapeutic vaccine trials among HIV-positive individuals.ObjectiveTo investigate the WTP in HIV therapeutic vaccine trials among Chinese HIV-infected patients.MethodsWe conducted a cross-sectional survey on HIV-positive inpatients and outpatients at Shanghai Public Health Center. A total of 447 participants were recruited into this study. Following an introduction with general information on HIV therapeutic vaccine and its potential effectiveness and side effects, each participant completed a questionnaire in a self-administered form. The questionnaires covered demographics, high-risk behaviors, clinical characteristics and willingness to participate in HIV therapeutic vaccine trial.ResultsThe overall willingness to participate in HIV therapeutic vaccine trials was 91.5%. Interestingly, multivariate logistic regression analyses demonstrated that the willingness was higher for those sexually infected by HIV (odds ratio [OR]: 4.36; 95% confidence interval [CI]: 1.53–12.41), diagnosed as HIV-1 infection for greater than 5 years (OR: 7.12, 95% CI: 1.83–27.76), and with the presence of infectious complications (OR: 2.75; 95% CI: 1.02–7.45). The primary reason for participation was to delay or reduce antiretroviral treatment (ART) and to avoid ART side effects (76.6%), and then followed by delaying disease progression (74.9%), increasing immune response to suppress opportunistic infections (57.7%) and preventing the development of drug resistance (37.1%). Reasons for unwillingness to participate mainly included concern for safety (37.0%), lack of knowledge on therapeutic vaccine (33.3%), and satisfaction with ART effectiveness (22.2%).ConclusionsThe WTP in HIV therapeutic vaccine trials was high among HIV-infected Chinese patients. HIV+ subjects who acquired infection through sexual contact and who were diagnosed for more than 5 years may represent a good candidate population for enrollment in therapeutic vaccine trials.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Willingness to Participate in HIV Therapeutic Vaccine Trials among HIV-Infected Patients on ART in China

et al. 2014

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“…Characterization of the BNAbs has provided key clues toward the design and development of both prophylactic and therapeutic vaccines (1)(2)(3)(4)(5)(6). A small proportion of individuals chronically infected with HIV-1 develop BNAbs (7)(8)(9)(10)(11)(12)(13)(14), and the isolation of several broad and potent neutralizing monoclonal antibodies (MAbs) from such individuals with distinct molecular specificities to viral envelope protein has been reported (15)(16)(17)(18)(19)(20)(21)(22)(23).…”

mentioning

confidence: 99%

Conformational Epitope-Specific Broadly Neutralizing Plasma Antibodies Obtained from an HIV-1 Clade C-Infected Elite Neutralizer Mediate Autologous Virus Escape through Mutations in the V1 Loop

Patil

Kumar

Deshpande

et al. 2016

J Virol

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Broadly neutralizing antibodies isolated from infected patients who are elite neutralizers have identified targets on HIV-1 envelope (Env) glycoprotein that are vulnerable to antibody neutralization; however, it is not known whether infection established by the majority of the circulating clade C strains in Indian patients elicit neutralizing antibody responses against any of the known targets. In the present study, we examined the specificity of a broad and potent cross-neutralizing plasma obtained from an Indian elite neutralizer infected with HIV-1 clade C. This plasma neutralized 53/57 (93%) HIV pseudoviruses prepared with Env from distinct HIV clades of different geographical origins. Mapping studies using gp120 core protein, single-residue knockout mutants, and chimeric viruses revealed that G37080 broadly cross-neutralizing (BCN) plasma lacks specificities to the CD4 binding site, gp41 membrane-proximal external region, N160 and N332 glycans, and R166 and K169 in the V1-V3 region and are known predominant targets for BCN antibodies. Depletion of G37080 plasma with soluble trimeric BG505-SOSIP.664 Env (but with neither monomeric gp120 nor clade C membrane-proximal external region peptides) resulted in significant reduction of virus neutralization, suggesting that G37080 BCN antibodies mainly target epitopes on cleaved trimeric Env. Further examination of autologous circulating Envs revealed the association of mutation of residues in the V1 loop that contributed to neutralization resistance. In summary, we report the identification of plasma antibodies from a clade C-infected elite neutralizer that mediate neutralization breadth via epitopes on trimeric gp120 not yet reported and confer autologous neutralization escape via mutation of residues in the V1 loop. IMPORTANCEA preventive vaccine to protect against HIV-1 is urgently needed. HIV-1 envelope glycoproteins are targets of neutralizing antibodies and represent a key component for immunogen design. The mapping of epitopes on viral envelopes vulnerable to immune evasion will aid in defining targets of vaccine immunogens. We identified novel conformational epitopes on the viral envelope targeted by broadly cross-neutralizing antibodies elicited in natural infection in an elite neutralizer infected with HIV-1 clade C. Our data extend our knowledge on neutralizing epitopes associated with virus escape and potentially contribute to immunogen design and antibody-based prophylactic therapy.

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“…7 The search for an HIV vaccine was seen as the logical solution to the burgeoning epidemic soon after the discovery of HIV, but early enthusiasm became muted as the realities of the challenge became evident. [8][9][10] Nevertheless, there are scientific reasons why there is hope that an HIV vaccine will be developed.…”

Section: Need For Vaccinementioning

confidence: 99%

“…A prime-boost strategy (RV144), utilizing canarypox vector prime + monomeric gp120 boost, has had the only positive clinical efficacy data to date for prevention of infection, albeit with a modest 31% efficacy in heterosexuals at moderate risk for infection. 7 The regimen was a heterologous prime-boost, i.e., 4 doses of one vaccine was boosted by 2 doses containing both vaccines. Although this result is not enough to qualify the vaccine for licensure, RV144 has provided very useful pointers for a way forward.…”

Section: Need For Vaccinementioning

confidence: 99%

Hiv

Chawla¹,

Sahoo²,

Jain³

et al. 2013

Human Vaccines & Immunotherapeutics

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Getting to zero: zero new HIV infections, zero deaths from AIDS-related illness, zero discrimination is the theme of World AIDS Day 2012. Given the spread of the epidemic today, getting to zero may sound difficult, but significant progress is underway. The total annual loss for the entire country due to HIV is 7% of GDP, which exceeds India's annual health expenditure in 2004. The additional loss due to loss of labor income and increased medical expenditure as measured by the external transfers, account for 5% of the country's health expenditure and 0.23% of GDP. Given that the HIV incidence rate is only 0.27% in India, these losses are quite staggering. Despite the remarkable achievements in development of anti-retroviral therapies against HIV and the recent advances in new prevention technologies, the rate of new HIV infections continue to outpace efforts on HIV prevention and control. Thus, the development of a safe and effective vaccine for prevention and control of AIDS remains a global public health priority and the greatest opportunity to eventually end the AIDS pandemic.

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Accelerating the development of a safe and effective HIV vaccine: HIV vaccine case study for the Decade of Vaccines

Cited by 27 publications

References 10 publications

Willingness to Participate in HIV Therapeutic Vaccine Trials among HIV-Infected Patients on ART in China

Willingness to Participate in HIV Therapeutic Vaccine Trials among HIV-Infected Patients on ART in China

Conformational Epitope-Specific Broadly Neutralizing Plasma Antibodies Obtained from an HIV-1 Clade C-Infected Elite Neutralizer Mediate Autologous Virus Escape through Mutations in the V1 Loop

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