HIV Vaccine

A human immunodeficiency virus type-1 (HIV-1) vaccine which is able to effectively prevent infection would be the most powerful method of extinguishing pandemic of the acquired immunodeficiency syndrome (AIDS). Yet, achieving such vaccine remains great challenges. The membrane-proximal external region (MPER) is a highly conserved region of the envelope glycoprotein (Env) gp41 subunit near the viral envelope surface, and it plays a key role in membrane fusion. It is also the target of some reported broadly neutralizing antibodies (bNAbs)...

Promising multi-dose HIV vaccine regimens are being tested in trials in South Africa. We estimated the potential epidemiological and economic impact of HIV vaccine campaigns compared to continuous vaccination, assuming that vaccine efficacy is transient and dependent on immune response. We used a dynamic economic mathematical model of HIV transmission calibrated to 2012 epidemiological data to simulate vaccination with anticipated antiretroviral treatment scale-up in South Africa. We estimate that biennial vaccination with a 70% efficacious vaccine reaching 20% of the sexually active population could prevent 480,000-650,000 HIV infections (13...

The discovery that humans can produce potent broadly neutralizing antibodies (bNAbs) to several different epitopes on the HIV-1 spike has reinvigorated efforts to develop an antibody-based HIV-1 vaccine. Antibody cloning from single cells revealed that nearly all bNAbs show unusual features that could help explain why it has not been possible to elicit them by traditional vaccination and instead would require a sequence of different immunogens. This idea is supported by experiments with genetically modified immunoglobulin (Ig) knock-in mice...

The successful establishment of humoral memory response depends on at least two layers of defense. Pre-existing protective antibodies secreted by long-lived plasma cells act as a first line of defense against reinfection ("constitutive humoral memory"). Previously, a second line of defense in which pathogen-experienced memory B cells are rapidly reactivated to produce antibodies ("reactive humoral memory"), was considered as simply a back-up system for the first line (particularly for re-infection with homologous viruses)...

Strain-specific neutralizing antibodies develop in all human immunodeficiency virus type 1 (HIV-1)-infected individuals. However, only 10-30% of infected individuals produce broadly neutralizing antibodies (bNAbs). Identification and characterization of these bNAbs and understanding their evolution dynamics are critical for obtaining useful clues for the development of an effective HIV vaccine. Very recently, we published a study in which we identified 12 HIV-1 subtype C-infected individuals from India whose plasma showed potent and broad cross-clade neutralization (BCN) ability (1)...

In the absence of an effective and safe vaccine against HIV-1, the administration of broadly neutralizing antibodies (bNAbs) represents a logical alternative approach to prevent virus transmission. Here, we introduced two mutations encoding amino acid substitutions (M428L and N434S, collectively referred to as 'LS') into the genes encoding the crystallizable fragment domains of the highly potent HIV-specific 3BNC117 and 10-1074 bNAbs to increase their half-lives and evaluated their efficacy in blocking infection following repeated low-dose mucosal challenges of rhesus macaques (Macaca mulatta) with the tier 2 SHIVAD8-EO ...

Although effective antibody-based vaccines have been developed against multiple viruses, such approaches have so far failed for the human immunodeficiency virus type 1 (HIV-1). Despite the success of anti-retroviral therapy (ART) that has turned HIV-1 infection into a chronic disease and has reduced the number of new infections worldwide, a vaccine against HIV-1 is still urgently needed. We discuss here the major reasons for the failure of "classical" vaccine approaches, which are mostly due to the biological properties of the virus itself...

BACKGROUND: Herpes zoster (HZ) occurs at a higher age-specific rate in people living with HIV (PLWH) than in the general population. We implemented a quality improvement study to assess herpes zoster vaccine (HZV) usage among PLWH, assess HZV usage after additional reminders/prompts, and identify barriers to HZV among older PLWH. METHODS: HZV rates in PLWH were determined in six institutions with varying payment structures. For the intervention, Part 1, PLWH eligible for HZV at the University of Colorado were identified, and providers were notified of patient eligibility...

Background: Adults living with HIV are at increased risk for anal and oropharyngeal cancer caused by human papillomavirus (HPV). The efficacy of HPV vaccines in this population is unknown. Methods: Phase 3, double-blind, randomized controlled trial. We assigned HIV-infected adults age 27 or older to the quadrivalent HPV (Types 6, 11, 16, 18) vaccine or placebo (1:1) stratified by sex and presence of anal high-grade squamous intraepithelial lesions on biopsy (bHSIL)...

The protective efficacy of human immunodeficiency virus-1 (HIV-1) antibodies (Abs) remains mostly correlated with their in vitro neutralizing activity engaging their Fab region. However, anti-HIV-1 Abs also mediate a broad array of Fc-mediated effector functions including Ab-dependent cellular cytotoxicity (ADCC), which depend primarily on the Ab isotype. While ADCC is commonly associated with HIV-1 gp120 envelope-specific IgGs, whether IgAs, especially those targeting the HIV-1 gp41 envelope, also mediate ADCC remains elusive...

HIV-specific T-cell responses play a key role in controlling HIV infection, and therapeutic vaccines for HIV that aim to improve viral control will likely need to improve on the T-cell responses induced by infection. However, in the setting of chronic infection, an effective therapeutic vaccine must overcome the enormous viral genetic diversity and the presence of pre-existing T-cell responses that are biased toward immunodominant T-cell epitopes that can readily mutate to evade host immunity and thus potentially provide inferior protection...

Background: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share common risk factors. The parallel description of their frequency over time may help capture their similarities and differences. Methods: Using data from the National Transfusion Center of Abidjan, we estimated the following over a 20-year period: (1) the prevalence of HIV and hepatitis B surface antigen (HBsAg) positivity at first contact; and (2) the incidence of HIV and HBsAg seroconversion in negative first-time blood donors...

A vaccination regimen capable of eliciting potent and broadly neutralizing antibodies (bNAbs) remains an unachieved goal of the HIV-1 vaccine field. Here we report the immunogenicity of longitudinal prime/boost vaccination regimens over a period of 200 weeks in guinea pigs with a panel of HIV-1 envelope (Env) gp140 protein immunogens. We assessed vaccine regimens that included a monovalent clade C gp140 regimen (C97), a tetravalent regimen consisting of four clade C gp140s (4C), and a tetravalent regimen consisting of a clade A, B, C, and mosaic gp140 (ABCM)...

Professional antigen presenting cells (APC: myeloid dendritic cells (DC) and macrophages (MΦ); B lymphocytes) mediate highly efficient HIV-1 infection of CD4+ T cells, termed trans infection, that could contribute to HIV-1 pathogenesis. We have previously shown that lower cholesterol content in DC and B lymphocytes is associated with a lack of HIV-1 trans infection in HIV-1 infected nonprogressors (NP). Here we assessed whether HIV-1 trans infection mediated by another major APC, MΦ, is deficient in NP due to altered cholesterol metabolism...

BACKGROUND: HIV/AIDS remains a leading cause of death in adolescents (aged 15 - 25 years), and in sub-Saharan Africa HIV-related deaths continue to rise in this age group despite a decline in both adult and paediatric populations. This is attributable in part to high adolescent infection rates and supports the urgent need for more efficacious prevention strategies. In particular, an even partially effective HIV vaccine, given prior to sexual debut, is predicted to significantly curb adolescent infection rates...

Since preexisting immunity and enhanced infection rates in a clinical trial of an HIV vaccine have raised some concerns on adenovirus (Ad) serotype 5-based vaccines, we evaluated the subgroup D adenovirus serotype Ad19a for its suitability as novel viral vector vaccine against mucosal infections. In BALB/c mice, we compared the immunogenicity and efficacy of E1/E3-deleted Ad19a vectors encoding the influenza A virus (IAV)-derived antigens hemagglutinin (HA) and nucleoprotein (NP) to the most commonly used Ad5 vectors...

Development of a vaccine against herpes simplex virus type 2 (HSV-2), a life-long sexually-transmitted infection (STI), would be a major step forward in improving global sexual and reproductive health. In this review, we identified published literature of dynamic mathematical models assessing the impact of either prophylactic or therapeutic HSV-2 vaccination at the population level. We compared each study's model structure and assumptions as well as predicted vaccination impact. We examined possible causes of heterogeneity across model predictions, key gaps, and the implications of these findings for future modelling efforts...

BACKGROUND: Men who have sex with men (MSM) are at risk for cancers attributable to human papillomavirus (HPV), including oropharyngeal cancer. HPV vaccination is recommended for U.S. MSM through age 26 years. Oral HPV infection is associated with oropharyngeal cancer. We determined oral HPV prevalence and risk factors among young MSM. METHODS: The Young Men's HPV study enrolled MSM aged 18-26 years from clinics in Chicago and Los Angeles during 2012-2014. Participants self-reported demographics, sexual behaviors, vaccination and HIV status...

OBJECTIVES: To identify factors that predispose HIV-exposed uninfected infants (HEUs) to higher incidence of severe infections, hospitalization and death in the first 6 to 24 months of life compared with HEUs with and without lower respiratory tract infection (LRTI) in the first 6 months of life. DESIGN: Nested case-control study of 107 LRTI+ infants enrolled in the NISDI Perinatal and LILAC studies with and 140 LRTI- in the first 6 months of, matched by date and place of birth...

OBJECTIVE: Postinfection HIV viral control and immune correlates analysis of the RV144 vaccine trial indicate a potentially critical role for Fc receptor-mediated antibody functions. However, the influence of functional antibodies in clade C infection is largely unknown. DESIGN: Plasma samples from 361 chronic subtype C-infected, antiretroviral therapy-naïve participants were tested for their HIV-specific isotype and subclass distributions, along with their Fc receptor-mediated functional potential...