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Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals.

ABSTRACT: Broadly Cross clade Neutralizing (BCN) antibodies are recognized as potential therapeutic tools and leads for the design of a vaccine that can protect human beings against various clades of Human Immunodeficiency Virus (HIV). In the present study, we screened plasma of 88 HIV-1 infected ART naïve individuals for their neutralization potential using a standard panel of 18 pseudoviruses belonging to different subtypes and different levels of neutralization. We identified 12 samples with good breadth of neutralization (neutralized >90% of the viruses). Four of these samples neutralized even the difficult-to-neutralize tier-3 pseudoviruses with great potency (GMT?>?600). Analysis of neutralization specificities indicated that four samples had antibodies with multiple epitope binding specificities, viz. CD4-binding site (CD4BS), glycans in the V1/V2 and V3 regions and membrane proximal external region (MPER). Our findings indicate the strong possibility of identifying highly potent bNAbs with known or novel specificities from HIV-1 subtype C infected individuals from India that can be exploited as therapeutic tools or lead molecules for the identification of potential epitopes for design of a protective HIV-1 vaccine.

SUBMITTER: Cheedarla N

PROVIDER: S-EPMC5402285 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals.

Cheedarla Narayanaiah N Precilla K Lucia KL Babu Hemalatha H Vijayan K K Vidya KKV Ashokkumar Manickam M Chandrasekaran Padmapriyadarsini P Kailasam Nandagopal N Sundaramurthi Jagadish Chandrabose JC Swaminathan Soumya S Buddolla Viswanath V Vaniambadi S Kalyanaraman SK Ramanathan V D VD Hanna Luke Elizabeth LE

Scientific reports 20170424

Broadly Cross clade Neutralizing (BCN) antibodies are recognized as potential therapeutic tools and leads for the design of a vaccine that can protect human beings against various clades of Human Immunodeficiency Virus (HIV). In the present study, we screened plasma of 88 HIV-1 infected ART naïve individuals for their neutralization potential using a standard panel of 18 pseudoviruses belonging to different subtypes and different levels of neutralization. We identified 12 samples with good bread ...[more]

PMID: 28436427

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Project description:Despite the success of COVID-19 vaccines in preventing infection and/or severe disease, there has been an increase in SARS-CoV-2 infections in vaccinated individuals owing to the waning vaccine-derived immunity, and the emergence of new variants which encode escape mutations in Spike. Following breakthrough infection in vaccinated individuals, an increase in neutralization breadth has been observed in sera/plasma. However, how exposure to a heterologous Spike broadens the neutralizing response at the monoclonal antibody (mAb) level is not fully understood. Through isolation of 119 mAbs from three individuals receiving two doses of BNT162b2 vaccine before becoming Delta or Omicron/BA.1 infected, we show that serum breadth occurs due to the presence of somatically mutated mAbs with broad neutralization activity indicative of re-activation and maturation of B cells generated through previous COVID-19 vaccination. Isolated mAbs frequently show reduced neutralization of current circulating variants including BA.2.75.2, XBB, XBB.1.5, and BQ.1.1 confirming continuous selective pressure on Spike to evolve and evade neutralization. However, isolation of mAbs that display effective cross-neutralization against all variants indicates the presence of conserved epitopes on the receptor binding domain and a lesser extent the N-terminal domain. These findings have implications for the selection of Spike antigens for next-generation COVID-19 vaccines. IMPORTANCE With the emergence of SARS-CoV-2 viral variants, there has been an increase in infections in vaccinated individuals. Here, we isolated monoclonal antibodies (mAbs) from individuals experiencing a breakthrough infection (Delta or BA.1) to determine how exposure to a heterologous Spike broadens the neutralizing antibody response at the monoclonal level. All mAbs isolated had reactivity to the Spike of the vaccine and infection variant. While many mAbs showed reduced neutralization of current circulating variants, we identified mAbs with broad and potent neutralization of BA.2.75.2, XBB, XBB.1.5, and BQ.1.1 indicating the presence of conserved epitopes on Spike. These results indicate that variant-based vaccine boosters have the potential to broaden the vaccine response.

Dataset Information

Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals.

Publications

Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals.

Similar Datasets

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