Background: Elite-neutralizer-derived HIV-1 envelopes (Envs), which induce broadly neutralizing antibodies (bnAbs), can inform HIV-1 vaccine design by serving as templates for bnAb-eliciting vaccines. Since single Env-based immunizations are insufficient to induce bnAb responses, sequential regimens using multivalent immunogens or Env cocktails hold greater promise. This underscores the need to develop stable Env trimers from diverse HIV-1 strains, particularly clade-C, which accounts for 50% of global infections and over 90% in India and South Africa.
View Article and Find Full Text PDFVarious design platforms are available to stabilize soluble HIV-1 envelope (Env) trimers, which can be used as antigenic baits and vaccine antigens. However, stabilizing HIV-1 clade C trimers can be challenging. Here, we stabilized an HIV-1 clade C trimer based on an Env isolated from a pediatric elite-neutralizer (AIIMS_329) using multiple platforms, including SOSIP.
View Article and Find Full Text PDFThe structural and characteristic features of HIV-1 broadly neutralizing antibodies (bnAbs) from chronically infected pediatric donors are currently unknown. Herein, we characterized a heavy chain matured HIV-1 bnAb 44m, identified from a pediatric elite-neutralizer. Interestingly, in comparison to its wild-type AIIMS-P01 bnAb, 44m exhibited moderately higher level of somatic hypermutations of 15.
View Article and Find Full Text PDFIn this Review, we have addressed some recent developments in the discovery and applications of anti-human immunodeficiency virus type- 1 (HIV-1) broadly neutralizing antibodies (bnAbs) isolated from infected adults and children. The recent developments in human antibody isolation technologies have led to the discovery of several highly potent anti-HIV-1 bnAbs. Herein, we have discussed the characteristics of recently identified bnAbs directed at distinct epitopes of HIV-1, in addition to the existing antibodies, from adults and children and have shed light on the benefits of multispecific HIV-1 bnAbs and their role in the design of polyvalent vaccines.
View Article and Find Full Text PDFCross-reactivity among the two diverse viruses is believed to originate from the concept of antibodies recognizing similar epitopes on the two viral surfaces. Cross-reactive antibody responses have been seen in previous variants of SARS and SARS-CoV-2, but little is known about the cross reactivity with other similar RNA viruses like HIV-1. In the present study, we examined the reactivity the SARS-CoV-2 directed antibodies, via spike, immunized mice sera and demonstrated whether they conferred any cross-reactive neutralization against HIV-1.
View Article and Find Full Text PDFCross-reactive epitopes (CREs) are similar epitopes on viruses that are recognized or neutralized by same antibodies. The S protein of SARS-CoV-2, similar to type I fusion proteins of viruses such as HIV-1 envelope (Env) and influenza hemagglutinin, is heavily glycosylated. Viral Env glycans, though host derived, are distinctly processed and thereby recognized or accommodated during antibody responses.
View Article and Find Full Text PDFThe spike protein of the SARS-CoV-2 virus is the foremost target for the designing of vaccines and therapeutic antibodies and also acts as a crucial antigen in the assessment of COVID-19 immune responses. The enveloped viruses; such as SARS-CoV-2, Human Immunodeficiency Virus-1 (HIV-1) and influenza, often hijack host-cell glycosylation pathways and influence pathobiology and immune selection. These glycan motifs can lead to either immune evasion or viral neutralization by the production of cross-reactive antibodies that can lead to antibody-dependent enhancement (ADE) of infection.
View Article and Find Full Text PDFProtective antibody responses to human immunodeficiency virus (HIV)-1 infection evolve only in a fraction of infected individuals by developing broadly neutralizing antibodies (bnAbs) and/or effector functions such as antibody-dependent cellular cytotoxicity (ADCC). HIV-1 chronically infected adults and children on combination antiretroviral therapy (cART) showed a reduction in ADCC activity and improvement in HIV-1 specific neutralizing antibody (nAb) responses. Early initiation of cART in infected adults is found to be beneficial in reducing the viral load and delaying disease progression.
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