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P01.17 LB

Neutralizing antibodies elicited in rabbits by patient-derived Env trimer immunization


Neutralizing antibodies elicited in rabbits by patient-derived Env trimer immunization

L Heyndrickx1, G Stewart-Jones2, H Schuitemaker3, E Bowles2, L Buonaguro4, M Jansson5, B Grevstad6, L Vinner6, M Ramaswamy7, P Biswas8, G Scarlatti8, G Vanham1, A Fomsgaard6 for the NGIN Consortium*.

1 Virology Unit, Institute of Tropical Medicine, Antwerp, Belgium, 2 Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford University, UK, 3 Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, The Netherlands, 4 Molecular Biology and Viral Oncogenesis Unit & AIDS Reference Center, Istituto Nazionale Tumori, Naples, Italy, 5 Department of Laboratory Medicine, University of Lund, Sweden, 6 Statens Serum Institut, Copenhagen, Denmark, 7 National Institute for Biological Standards and Control, Hertfordshire, UK, 8 San Raffaele Scientific Institute, Milan, Italy. * Work supported by EC-FP7-grant NGIN_201433

Summary

Broadly neutralizing antibodies (bNAbs), that cross react with diverse HIV-1 subtypes, develop in some (10-30%) individuals during chronic infection. Immunization strategies that utilize patient-derived envelopes (Env) may result in improved bNAb development. Based on in-vitro neutralizing activity in serum, four patients with bNAbs were selected. From two patients (AMD358 and AMD446 both subtype B) Env sequences of early HIV-1 variants, still sensitive to autologous neutralization, were used to generate soluble Envs as immunogens. From patient ITM-1 (subtype A) both the earliest available (ITM1-4) and the predicted ‘ancestral’ Env (ITM_anc), as based on 178 full-length env sequences spanning 11 years, were used. The Env from the remaining patient (UG) was from an asymptomatic subtype A infected pregnant women. The rationale for this selection was based on the hypothesis that viral variants with specific Env structures must have elicited bNAb responses and may elicit these responses again in animals or humans if formulated into an appropriate vaccine immunogen.

We show that gp140 trimers based on HIV-1 variants of patients with bNAb in serum elicited gp120-IIIB specific IgG and NAb in rabbits, on the condition that enough immunogen was administrated in the presence of the adjuvant CAF01. Our results indicate that the development of HIV-1 Env specific NAb is dose-dependent, requires adjuvants and can be studied using the rabbit model for HIV vaccine studies.

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