HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees

نویسندگان

  • Nicole L Yates
  • Allan C deCamp
  • Bette T Korber
  • Hua-Xin Liao
  • Carmela Irene
  • Abraham Pinter
  • James Peacock
  • Linda J Harris
  • Sheetal Sawant
  • Peter Hraber
  • Xiaoying Shen
  • Supachai Rerks-Ngarm
  • Punnee Pitisuttithum
  • Sorachai Nitayapan
  • Phillip W Berman
  • Merlin L Robb
  • Giuseppe Pantaleo
  • Susan Zolla-Pazner
  • Barton F Haynes
  • S Munir Alam
  • David C Montefiori
  • Georgia D Tomaras
چکیده

Induction of broadly cross-reactive antiviral humoral responses with the capacity to target globally diverse circulating strains is a key goal for HIV-1 immunogen design. A major gap in the field is the identification of diverse HIV-1 envelope antigens to evaluate vaccine regimens for binding antibody breadth. In this study, we define unique antigen panels to map HIV-1 vaccine-elicited antibody breadth and durability. Diverse HIV-1 envelope glycoproteins were selected based on genetic and geographic diversity to cover the global epidemic, with a focus on sexually acquired transmitted/founder viruses with a tier 2 neutralization phenotype. Unique antigenicity was determined by nonredundancy (Spearman correlation), and antigens were clustered using partitioning around medoids (PAM) to identify antigen diversity. Cross-validation demonstrated that the PAM method was better than selection by reactivity and random selection. Analysis of vaccine-elicited V1V2 binding antibody in longitudinal samples from the RV144 clinical trial revealed the striking heterogeneity among individual vaccinees in maintaining durable responses. These data support the idea that a major goal for vaccine development is to improve antibody levels, breadth, and durability at the population level. Elucidating the level and durability of vaccine-elicited binding antibody breadth needed for protection is critical for the development of a globally efficacious HIV vaccine.IMPORTANCE The path toward an efficacious HIV-1 vaccine will require characterization of vaccine-induced immunity that can recognize and target the highly genetically diverse virus envelope glycoproteins. Antibodies that target the envelope glycoproteins, including diverse sequences within the first and second hypervariable regions (V1V2) of gp120, were identified as correlates of risk for the one partially efficacious HIV-1 vaccine. To build upon this discovery, we experimentally and computationally evaluated humoral responses to define envelope glycoproteins representative of the antigenic diversity of HIV globally. These diverse envelope antigens distinguished binding antibody breadth and durability among vaccine candidates, thus providing insights for advancing the most promising HIV-1 vaccine candidates.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Epitope Specificity of Human Immunodeficiency Virus-1 Antibody Dependent Cellular Cytotoxicity [ADCC] Responses

Antibody dependent cellular cytotoxicity [ADCC] has been suggested to play an important role in control of Human Immunodeficiency Virus-1 [HIV-1] viral load and protection from infection. ADCC antibody responses have been mapped to multiple linear and conformational epitopes within the HIV-1 envelope glycoproteins gp120 and gp41. Many epitopes targeted by antibodies that mediate ADCC overlap wi...

متن کامل

Differences in the antibody response to human immunodeficiency virus-1 envelope glycoprotein (gp160) in infected laboratory workers and vaccinees.

Studies of the immune response to the human immunodeficiency virus (HIV) have been hampered by the antigenic diversity of the HIV envelope protein. In an effort to predict the efficacy of vaccination we have compared the systemic anti-envelope antibody response in seronegative volunteers immunized with recombinant gp160 (either in vaccinia or as soluble protein produced in baculovirus) derived ...

متن کامل

Immunization of macaques with soluble HIV type 1 and influenza virus envelope glycoproteins results in a similarly rapid contraction of peripheral B-cell responses after boosting.

The envelope glycoproteins (Env) represent a critical component of a successful antibody-mediated human immunodeficiency virus type 1 (HIV-1) vaccine. However, immunization with soluble Env was reported to induce short-lived antibody responses, suggesting that Env has unusual immunogenic properties. Here, we directly compared the magnitude and durability of B-cell responses induced by HIV-1 Env...

متن کامل

Levels of N-linked glycosylation on the V1 loop of HIV-1 Env proteins and their relationship to the antigenicity of Env from primary viral isolates.

A good understanding about the structure and function of the envelope glycoprotein (Env) from primary human immunodeficiency virus-1 (HIV-1) isolates is important in facilitating the development of effective neutralizing antibody responses as a component of an effective HIV-1 vaccine. In the current study, the antigenicity of a panel of diverse HIV-1 primary Env from different clades of HIV-1 G...

متن کامل

Antigenicity and immunogenicity of transmitted/founder, consensus, and chronic envelope glycoproteins of human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) vaccine development requires selection of appropriate envelope (Env) immunogens. Twenty HIV-1 Env glycoproteins were examined for their ability to bind human anti-HIV-1 monoclonal antibodies (MAbs) and then used as immunogens in guinea pigs to identify promising immunogens. These included five Envs derived from chronically infected individuals, each r...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 92  شماره 

صفحات  -

تاریخ انتشار 2018