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Structural insights into key sites of vulnerability on HIV-1 Env and influenza HA.

ABSTRACT: Human immunodeficiency virus-1 (HIV-1) envelope protein (Env) and influenza hemagglutinin (HA) are the surface glycoproteins responsible for viral entry into host cells, the first step in the virus life cycle necessary to initiate infection. These glycoproteins exhibit a high degree of sequence variability and glycosylation, which are used as strategies to escape host immune responses. Nonetheless, antibodies with broadly neutralizing activity against these viruses have been isolated that have managed to overcome these barriers. Here, we review recent advances in the structural characterization of these antibodies with their viral antigens that defines a few sites of vulnerability on these viral spikes. These broadly neutralizing antibodies tend to focus their recognition on the sites of similar function between the two viruses: the receptor-binding site and membrane fusion machinery. However, some sites of recognition are unique to the virus neutralized, such as the dense shield of oligomannose carbohydrates on HIV-1 Env. These observations are discussed in the context of structure-based design strategies to aid in vaccine design or development of antivirals.

SUBMITTER: Julien JP

PROVIDER: S-EPMC3479221 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Structural insights into key sites of vulnerability on HIV-1 Env and influenza HA.

Julien Jean-Philippe JP Lee Peter S PS Wilson Ian A IA

Immunological reviews 20121101 1

Human immunodeficiency virus-1 (HIV-1) envelope protein (Env) and influenza hemagglutinin (HA) are the surface glycoproteins responsible for viral entry into host cells, the first step in the virus life cycle necessary to initiate infection. These glycoproteins exhibit a high degree of sequence variability and glycosylation, which are used as strategies to escape host immune responses. Nonetheless, antibodies with broadly neutralizing activity against these viruses have been isolated that have m ...[more]

PMID: 23046130

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Project description:One of the newest strategies developed by the Global Influenza Strategy has been to broaden the composition of the current influenza vaccine formulations from trivalent products to quadrivalent products. This study aimed to assess the immunogenicity and safety of Quadrivalent Influenza HA vaccine (QIV) compared with Trivalent Influenza HA vaccine (TIV) and to evaluate three consecutive batches of QIV equivalence in Indonesian children and adults. This was an experimental, randomized, double blind, four arm parallel group bridging study involving unprimed healthy children and adults aged 9-40 years. A total of 540 subjects were enrolled in this study and randomized into four arm groups. Each subject received one dose of TIV or QIV with three different batch codes. Serology tests were performed at baseline and 28 days after vaccination. Hemagglutination inhibition (HI) antibody titers were analyzed for Geometric Mean Titer (GMT), seroprotection, and seroconversion rates. Solicited, unsolicited, and serious adverse events were observed up to 28 days after vaccination. A total of 537 subjects completed the study per protocol and were analyzed for immunogenicity criteria. All randomized subjects were analyzed for safety criteria. The percentage of the subjects with anti-HI titer ≥1:40 28 days after QIV vaccination was 99.5% for A/H1N1; 99.5% for A/H3N2; 93.1% for B/Texas, and 99.0% for B/Phuket. The seroprotection, GMT, and seroconversion rates of QIV were not significantly different from those of TIV for the common vaccine strains (p > 0.01) and were significantly different from those of TIV for the added B/Phuket strains (p < 0.01). Most solicited injection-site and systemic reactions with either vaccine were mild to moderate and resolved within a few days. Antibody response to QIV were equivalence among vaccine batches and comparable between age groups for each of the 4 strains. QIV was immunogenic and well-tolerated and had immunogenicity and safety profiles compared with TIV for all common strains. The immunogenicity of the three batches of QIV was equivalent for the four strains. Trial registration. Clinical Trial registration: NCT03336593.

Dataset Information

Structural insights into key sites of vulnerability on HIV-1 Env and influenza HA.

Publications

Structural insights into key sites of vulnerability on HIV-1 Env and influenza HA.

Similar Datasets

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