Humoral Response to the HIV-1 Envelope V2 Region in a Thai Early Acute Infection Cohort

Hung V Trinh; Neelakshi Gohain; Peter T Pham; Christopher Hamlin; Hongshuo Song; Eric Sanders-Buell; Meera Bose; Leigh A Eller; Swati Jain; Gherman Uritskiy; Venigalla B Rao; Sodsai Tovanabutra; Nelson L Michael; Merlin L Robb; M Gordon Joyce; Mangala Rao

doi:10.3390/cells8040365

Humoral Response to the HIV-1 Envelope V2 Region in a Thai Early Acute Infection Cohort

Cells. 2019 Apr 19;8(4):365. doi: 10.3390/cells8040365.

Authors

Hung V Trinh^{1

2}, Neelakshi Gohain^{3

4}, Peter T Pham^{5

6}, Christopher Hamlin^{7

8}, Hongshuo Song^{9

10}, Eric Sanders-Buell^{11

12}, Meera Bose^{13

14}, Leigh A Eller^{15

16}, Swati Jain, Gherman Uritskiy, Venigalla B Rao, Sodsai Tovanabutra^{17

18}, Nelson L Michael¹⁹, Merlin L Robb^{20

21}, M Gordon Joyce^{22

23}, Mangala Rao²⁴

Affiliations

¹ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. [email protected].
² Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA. [email protected].
³ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. [email protected].
⁴ Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA. [email protected].
⁵ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. [email protected].
⁶ Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA. [email protected].
⁷ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. [email protected].
⁸ Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA. [email protected].
⁹ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. [email protected].
¹⁰ Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA. [email protected].
¹¹ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. [email protected].
¹² Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA. [email protected].
¹³ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. [email protected].
¹⁴ Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA. [email protected].
¹⁵ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. [email protected].
¹⁶ Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA. [email protected].
¹⁷ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. [email protected].
¹⁸ Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA. [email protected].
¹⁹ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. [email protected].
²⁰ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. [email protected].
²¹ Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA. [email protected].
²² U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. [email protected].
²³ Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD 20817, USA. [email protected].
²⁴ U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. [email protected].

Abstract

Reduced risk of HIV-1 infection correlated with antibody responses to the envelope variable 1 and 2 regions in the RV144 vaccine trial. To understand the relationship between antibody responses, V2 sequence, and structure, plasma samples (n = 16) from an early acute HIV-1 infection cohort from Thailand infected with CRF01_AE strain were analyzed for binding to V2 peptides by surface plasmon resonance. Five participants with a range of V2 binding responses at week 24 post-infection were further analyzed against a set of four overlapping V2 peptides that were designed based on envelope single-genome amplification. Antibody responses that were relatively consistent over the four segments of the V2 region or a focused response to the C-strand (residues 165-186) of the V2 region were observed. Viral escape in the V2 region resulted in significantly reduced antibody binding. Structural modeling indicated that the C-strand and the sites of viral variation were highly accessible in the open conformation of the HIV-1 Env trimer. V2 residues, 165-186 are preferentially targeted during acute infection. Residues 169-184 were also preferentially targeted by the protective immune response in the RV144 trial, thus emphasizing the importance of these residues for vaccine design.

Keywords: CRF01_AE; HIV-1; RV217 prospective study; V2 region; acute infection; immune response; single genome amplification (SGA); structural biology; surface plasmon resonance (SPR); transmitted/founder (T/F) virus.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

AIDS Vaccines / administration & dosage
AIDS Vaccines / immunology*
Amino Acid Sequence / genetics
Antibodies, Neutralizing / blood
Cohort Studies
HIV Antibodies / immunology*
HIV Envelope Protein gp120 / genetics
HIV Envelope Protein gp120 / immunology*
HIV Envelope Protein gp120 / ultrastructure
HIV Infections / immunology*
HIV Seropositivity
HIV-1 / immunology*
Humans
Immunity, Humoral

Substances

AIDS Vaccines
Antibodies, Neutralizing
HIV Antibodies
HIV Envelope Protein gp120