New Tools to Assess HIV Broadly Neutralizing Antibodies

Broadly neutralizing antibodies (bnAbs) are a focus of HIV research as a possible target for vaccine development. In 2021, infusions of bnAbs were shown to neutralize circulating HIV, however development of vaccine immunogens capable of eliciting potent bnABs has posed a significant challenge to HIV researchers.¹

Identification and development of anti-HIV-1 vaccine immunogens or anti-HIV-1 bnAbs requires the availability of novel tools to evaluate their effectiveness.

A set of vectors is now available from BEI Resources for both in vivo and in vitro studies to assess the effectiveness of anti-HIV-1 vaccine immunogens or anti-HIV-1 bnAbs. This set includes two clones, pSHIV AD8EO (HRP-20278), a pathogenic CCR5 (R5)-tropic SHIV molecular clone derived from SHIVAD8, and R5-tropic pSHIV DH12-v3AD8 (HRP-20279), which was constructed by inserting the entire 33-amino acid gp120 V3 coding region of AD8EO into the background of SHIVDH12-CL-7 (a molecularly cloned derivative of CXCR4-tropic SHIV DH12 virus). Clone pSHIV AD8EO produces sustained levels of plasma viremia in inoculated macaques, exhibits a Tier 2 neutralization sensitivity phenotype, generates resistant variants in bnAb and ART-treated animals and causes irreversible depletion of CD4+ T cells, leading to symptomatic immunodeficiency in infected monkeys.^2,3 Clone R5-tropic pSHIV DH12-v3AD8 demonstrates robust replication kinetics during infection of rhesus monkey PBMCs.⁴ Also included in this set is vector pCK15-3-3 (HRP-20280), designed to express the AD8EO envelope for pseudovirus construction by co-transfection with the HIV-1 pNL4-3ΔEnv non-infectious molecular clone (HRP-20281).⁵

References:

1. "Corey, L., et al. “Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition.” N. Engl. J. Med. 384 (2021): 1003-1014. PubMed: 33730454.

2. hingai, M., et al. “Most Rhesus Macaques Infected with the CCR5-Tropic SHIV(AD8) Generate Cross-Reactive Antibodies that Neutralize Multiple HIV-1 Strains.” Proc. Acad. Sci. USA 109 (2012): 19769-74. PubMed: 23129652.

3. Shingai, M., et al. “Passive Transfer of Modest Titers of Potent and Broadly Neutralizing Anti-HIV Monoclonal Antibodies Block SHIV Infection in Macaques.” J. Exp. Med. 211 (2014): 2061-2074. PubMed: 25155019.

4. Sadjadpour, R., et al. “Induction of Disease by a Molecularly Cloned Highly Pathogenic Simian Immunodeficiency Virus/Human Immunodeficiency Virus Chimera is Multigenic.” J. Virol. 78 (2004): 5513- 5519. PubMed: 15113931.

5. Adachi, A., et al. “Production of Acquired Immunodeficiency Syndrome-Associated Retrovirus in Human and Nonhuman Cells Transfected with an Infectious Molecular Clone.” J. Virol. 59 (1986): 284-291. PubMed: 3016298.