Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial

Kijak, Gustavo H.; Tovanabutra, Sodsai; Rerks-Ngarm, Supachai; Nitayaphan, Sorachai; Eamsila, Chirapa; Kunasol, Prayura; Khamboonruang, Chirasak; Thongcharoen, Prasert; Namwat, Chawetsan; Premsri, Nakorn; Benenson, Michael W.; Morgan, Patricia; Bose, Meera; Sanders‐Buell, Eric; Paris, Robert; Robb, Merlin L.; Birx, Deborah L.; Souza, Mark S. de; McCutchan, Francine E.; Michael, Nelson L.; Kim, Jerome H.

doi:10.1128/jvi.03070-12

Cited by 27 publications

(25 citation statements)

References 81 publications

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“…Approximately 90% of the incident infections in RV144 were infections with CRF01_AE, the predominant circulating strain in much of Southeast Asia (78,79). A sieve analysis identified two vaccine-associated genetic signatures in V2 corresponding to sites 169 and 181, further supporting the hypothesis that vaccinationinduced immune responses directed against the V2 loop were associated with protection (9).…”

Section: Rv144 Prime-boost Efficacy Trialmentioning

confidence: 67%

Nonneutralizing Functional Antibodies: a New “Old” Paradigm for HIV Vaccines

Excler¹,

Ake²,

Robb³

et al. 2014

Clin. Vaccine Immunol.

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106

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Animal and human data from various viral infections and vaccine studies suggest that nonneutralizing antibodies (nNAb) without neutralizing activity in vitro may play an important role in protection against viral infection in vivo. This was illustrated by the recent human immunodeficiency virus (HIV) RV144 vaccine efficacy trial, which demonstrated that HIV-specific IgG-mediated nNAb directed against the V2 loop of HIV type 1 envelope (Env) were inversely correlated with risk for HIV acquisition, while Env-specific plasma IgA-mediated antibodies were directly correlated with risk. However, tier 1 NAb in the subset of responders with a low level of plasma Env-specific IgA correlated with decreased risk. Nonhuman primate simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus (SHIV) challenge studies suggest that Env-mediated antibodies are essential and sufficient for protection. A comparison of immune responses generated in human efficacy trials reveals subtle differences in the fine specificities of the antibody responses, in particular in HIV-specific IgG subclasses. The underlying mechanisms that may have contributed to protection against HIV acquisition in humans, although not fully understood, are possibly mediated by antibody-dependent cell-mediated cytotoxicity (ADCC) and/or other nonneutralizing humoral effector functions, such as antibody-mediated phagocytosis. The presence of such functional nNAb in mucosal tissues and cervico-vaginal and rectal secretions challenges the paradigm that NAb are the predominant immune response conferring protection, although this does not negate the desirability of evoking neutralizing antibodies through vaccination. Instead, NAb and nNAb should be looked upon as complementary or synergistic humoral effector functions. Several HIV vaccine clinical trials to study these antibody responses in various prime-boost modalities in the systemic and mucosal compartments are ongoing. The induction of high-frequency HIV-specific functional nNAb at high titers may represent an attractive hypothesis-testing strategy in future HIV vaccine efficacy trials. The identification of immune markers that correlate with protection against infection or disease after vaccination (or natural infection) remains the "holy grail" for vaccine scientists, as these immune markers have the potential to expedite vaccine development and provide unique insights into the pathogenesis of infection. For most of the vaccines available today, a functional antibody response is the identified correlate of protection (1). In the cases of candidate preventive human immunodeficiency virus (HIV) vaccines and experimental vaccines against the closely related retrovirus simian immunodeficiency virus (SIV), recent studies have suggested an antibody correlate of risk or protection. However, these studies suggested an association with antibodies that did not mediate broad or potent neutralization (2-5).Transmission of HIV type 1 (HIV-1) occurs through homosexual or heterosexual intercourse, through inje...

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Section: Rv144 Prime-boost Efficacy Trialmentioning

confidence: 67%

Nonneutralizing Functional Antibodies: a New “Old” Paradigm for HIV Vaccines

Excler¹,

Ake²,

Robb³

et al. 2014

Clin. Vaccine Immunol.

Self Cite

106

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“…In Thailand, during the early years of the epidemic, subtype B (Western type B and Thai B or B’) was the most prevalent clade among PWID while CRF01_AE was frequent in people infected heterosexually (Deng et al, 2008; Kijak et al, 2013; Ou et al, 1993). The ancestor of Thai B or B’ existed around 1985 having diverged from subtype B and became the founder strain in South and Southeast Asia (Deng et al, 2008; Junqueira and Almeida, 2016; Li et al, 2010b).…”

Section: Molecular Epidemiology Of Hiv Among Pwid In Asiamentioning

confidence: 99%

Overview of HIV molecular epidemiology among people who inject drugs in Europe and Asia

Nikolopoulos

Kostaki

Paraskevis

2016

Infection, Genetics and Evolution

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HIV strains continuously evolve, tend to recombine and new circulating variants are being discovered. Novel strains complicate efforts to develop a vaccine against HIV and may exhibit higher transmission efficiency and virulence, and elevated resistance to antiretroviral agents. The United Nations Joint Programme on HIV/AIDS (UNAIDS) set an ambitious goal to end HIV as a public health threat by 2030 through comprehensive strategies that include epidemiological input as the first step of the process. In this context, molecular epidemiology becomes invaluable as it captures trends in HIV evolution rates that shape epidemiological pictures across several geographical areas. This review briefly summarizes the molecular epidemiology of HIV among people who inject drugs (PWID) in Europe and Asia. Following high transmission rates of subtype G and CRF14_BG among PWID in Portugal and Spain, two European countries, Greece and Romania, experienced recent HIV outbreaks in PWID that consisted of multiple transmission clusters including subtypes B, A, F1 and recombinants CRF14_BG and CRF35_AD. The latter was first identified in Afghanistan. Russia, Ukraine and other Former Soviet Union (FSU) states are still facing the devastating effects of epidemics in PWID produced by AFSU (also known as IDU-A), BFSU (known as IDU-B), and CRF03_AB. In Asia, CRF01_AE and subtype B (Western B and Thai B) travelled from PWID in Thailand to neighboring countries. Recombination hotspots in South China, Northern Myanmar, and Malaysia have been generating several intersubtype and inter-CRF recombinants (e.g. CRF07_BC, CRF08_BC, CRF33_01B etc.) increasing the complexity of HIV molecular patterns.

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“…Participants in this cohort were identified during early acute HIV-1 infection and immediately offered cART; they were also willing to undergo colonic biopsies (26, 27). This cohort represents a unique opportunity to investigate the effect of cART on the GI tract at the earliest time points clinically feasible after initial HIV infection.…”

Section: Introductionmentioning

confidence: 99%

Impact of early cART in the gut during acute HIV infection

Deléage¹,

Schuetz²,

Alvord³

et al. 2016

JCI Insight

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Early after HIV infection there is substantial depletion of CD4+ T cells in the gastrointestinal (GI) tract lamina propria (LP), with associated epithelial barrier damage, leading to microbial translocation and systemic inflammation and immune activation. In this study, we analyzed these early events in the GI tract in a cohort of Thai acute HIV-infected patients and determined the effect of early combination antiretroviral treatment (cART). HIV-uninfected and chronically and acutely HIV-infected patients at different Fiebig stages (I–V) underwent colonic biopsies and then received cART. Immunohistochemistry and quantitative image analysis were performed on cross-sectional and longitudinal colon biopsy specimens (day 0 to week 96) to measure GI tract damage (infiltration of polymorphonuclear cells), inflammation (M×1, TNF-α), immune activation (Ki-67), and the CD4+ T cell population in the LP. The magnitude of GI tract damage, immune activation, and inflammation was significantly increased, with significantly depleted CD4+ T cells in the LP in all acutely infected groups prior to cART compared with HIV-uninfected control participants. While most patients treated during acute infection resolved GI tract inflammation and immune activation back to baseline levels after 24 weeks of cART, most acutely infected participants did not restore their CD4+ T cells after 96 weeks of cART.

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Molecular Evolution of the HIV-1 Thai Epidemic between the Time of RV144 Immunogen Selection to the Execution of the Vaccine Efficacy Trial

Cited by 27 publications

References 81 publications

Nonneutralizing Functional Antibodies: a New “Old” Paradigm for HIV Vaccines

Nonneutralizing Functional Antibodies: a New “Old” Paradigm for HIV Vaccines

Overview of HIV molecular epidemiology among people who inject drugs in Europe and Asia

Impact of early cART in the gut during acute HIV infection

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