Adjuvant - a pharmacological agent that is added to a vaccine to enhance the immune response of the vaccine recipient.

Affinity maturation - the process by which B cells produce antibodies with increased affinity for antigen during an immune response.

Antibody - a protein molecule that is made and secreted by B cells in response to stimulation from antigens, such as viruses. Each antibody specifically binds to one antigen, which they target for neutralization or flag for destruction by white blood cells. The induction of neutralizing antibodies against HIV-1 is a key goal of an HIV-1 vaccine. See also broadly neutralizing antibodies, intermediate antibody, and recombinant monoclonal antibody.

Antibody-Virus Co-Evolution Project - a collaborative project of the Duke CHAVI-ID and the NIH Vaccine Research Center to isolate the evolution pathways of all known specificities of HIV-1 broadly neutralizing antibodies (BnAbs) and the evolution pathways of the founder HIV-1 virus that induced BnAbs in individuals with HIV-1 infection.

• Liao et al. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature. 2013 Apr 25; 496(7446):469-76.

Antigen - a foreign substance, such as a virus, that enters the body and induces an immune response. Similar to a lock and key, antigens specifically bind to their respective antibodies via the epitopes that are exposed on the surface of the antigen.

B cell precursors - B lineage cells that are produced in the bone marrow before maturing into B cells.

B Cell Lineage Vaccine Design - a vaccine strategy of the Duke CHAVI-ID that is based on targeting the unmutated common ancestor (UCA) and intermediate antibody (IA) of broadly neutralizing antibody lineages using Envs or Env subunits that are designed to optimally bind to UCAs and IAs. 

• Haynes BF, Kelsoe G, Harrison SC, Kepler TB. B-cell-lineage immunogen design in vaccine development with HIV-1 as a case study. Nat Biotechnol. 2012 May 7; 30(5): 423-33.

Binding affinity - the strength of the interaction between a single antigen binding site on an antibody and a single epitope on an antigen.

Broadly neutralizing antibodies (BnAbs) - antibodies that are capable of neutralizing a wide range of HIV-1 strains; however, they are rarely made during infection and are difficult to detect. The main focus of the Duke CHAVI-ID is to design immunogens that can be used in a vaccine to induce BnAbs for protection against a wide range of HIV-1 strains.

CH505 - the Env that was obtained from patient CH505 who developed neutralization breadth during follow-up from acute HIV-1 infection. This person was the first CHAVI 17 participant who was studied for antibody and viral co-evolution. See the Antibody-Virus Co-Evolution Project.

CHAVI 17 - 17 participants with acute HIV-1 infection in the CHAVI 001 study who developed neutralization breadth during follow-up.

Clonal lineage - a lineage of evolved mutated antibodies that are derived from a common unmutated ancestor antibody.

Deep Sequencing - a DNA sequencing method that is used to detect rare variants in viruses, bacteria, or cells by sequencing thousands of genomes from a single specimen. The Duke CHAVI-ID is using this technology to detect rare variants in B cell lineages that produce broadly neutralizing antibodies (BnAbs). The following instruments are currently being used for deep sequencing: 454 GS Junior (Roche), MiSeq (Illumina), and Ion Torrent PGM (Life Technologies).

Envelope (Env) - a viral protein that forms the viral envelope or surface of HIV-1.

Epitope - distinct molecular features on the surface of antigens that are recognized by the immune system. Also known as antigenic determinants. Antibodies target epitopes for antigen binding and neutralization.

Glycopeptide - peptides that contain glycans or carbohydrates. Glycopeptides have been synthetically produced to mimic regions of HIV-1 for binding with broadly neutralizing antibodies (BnAbs).

Gp41 (glycoprotein 41) - a transmembrane glycoprotein and a subunit of the HIV-1 envelope that assists in HIV-1 fusion to host cells.

Gp120 (glycoprotein 120) - a glycoprotein on the HIV-1 envelope that binds to CD4 cell receptors for virus entry into the cells.

HIV-1 diversity - the wide variety of HIV-1 subtypes. A successful HIV-1 vaccine must protect against all HIV-1 subtypes.

HIV-1 virus evolution - HIV-1 mutations that occur during infection. Please see the Antibody-Virus Co-Evolution Project.

HVTN082 - a phase II clinical trial that is being conducted by the HIV Vaccine Trials Network (HVTN) to test the safety and immunogenicity of a vaccine that was produced by the NIH Vaccine Research Center (same as HVTN204) in 4 pairs of twins (fraternal or identical). The effect of genetics on the antibody repertoires that are induced in response to the vaccine will be studied.

HVTN099 - a mosaic clinical trial that was designed by the Center for HIV/AIDS Vaccine Immunology (CHAVI) in collaboration with the Division of AIDS (DAIDS), the Bill and Melinda Gates Foundation, and the HIV Vaccine Trials Network (HVTN). Enrollment will start in the fall 2013.

• Santra S et al. Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys. Nat Med. 2010 Mar; 16(3):324-8.
• Barouch DH et al. Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys. Nat Med. 2010 Mar; 16(3):319-23.

HVTN204 - a phase II clinical trial that is being conducted by the HIV Vaccine Trials Network (HVTN) to test the safety and immunogenicity of the VRC DNA-rAd5 vaccine (DNA vaccine VRC-HIVDNA016-00-VP and adenoviral vector vaccine VRC-HIVADV014-00-VP).

Immunogen - an antigen in a substance, such as a vaccine, that may be recognized by the immune system and targeted for destruction. HIV-1 vaccine immunogens are designed to bind with broadly neutralizing antibodies (BnAbs) to ensure that a robust antibody response is available to protect against HIV-1 infection.

Intermediate antibody - antibodies in a clonal lineage that are evolved and intermediate, in between an unmutated common ancestor precursor and a mature mutated antibody.

Intermediate Env immunogens - recombinantly produced monomeric gp120 or gp120 subunit immunogens.

Membrane-anchored Env trimer - a cleavage-negative, membrane-bound HIV-1 Env trimer that is solubilized in detergents (as described in Mao et al., below) for reconstitution into liposomes for immunization studies.

• Mao Y, et al. Subunit organization of the membrane-bound HIV-1 envelope glycoprotein trimer. Nat Struct Mol Biol. 2012 Sep; 19(9):893-9.

Membrane proximal external region (MPER) - a region of the gp41 protein in the HIV-1 envelope. Rare neutralizing antibodies have been found to bind to the epitopes in this region. A key vaccine strategy of the Duke CHAVI-ID involves the production of an artificial virus particle with neutralizing epitopes for gp41 MPER.

Minimal Env immunogens - synthetic or recombinant immunogens that are designed to specifically and predominantly express a subdominant broadly neutralizing antibody (BnAb) epitope and to not, or minimally, express dominant non-neutralizing Env epitopes.

Recombinant monoclonal antibody (mAb) - an antibody that is produced from the rescued heavy and light chains of a single B cell using recombinant DNA techniques.

RNA Sequencing - is a sequencing technique that uses RNA as the template rather than DNA. The results show only the genes that are transcribed rather than the whole genome sequenced in DNA. This method is also called Whole Transcriptome Shotgun Sequencing.

RV144 - a phase III HIV vaccine efficacy trial that was conducted in Thailand, which consisted of a prime-boost combination of the ALVAC® HIV Vaccine and AIDSVAX® B/E. The Center for HIV/AIDS Vaccine Immunology (CHAVI) team led the case control study of RV144 and the subsequent studies of potentially protective antibodies.

• Haynes BF et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012 Apr 5; 366(14):1275-86.
• Montefiori DC et al. Magnitude and breadth of the neutralizing antibody response in the RV144 and Vax003 HIV-1 vaccine efficacy trials. J Infect Dis. 2012 Aug 1; 206(3):431-41.
• Bonsignori M et al. Antibody-dependent cellular cytotoxicity-mediating antibodies from an HIV-1 vaccine efficacy trial target multiple epitopes and preferentially use the VH1 gene family. J Virol. 2012 Nov; 86(21):11521-32.
• Liao HX et al. Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2. Immunity. 2013 Jan 24; 38(1):176-86.
• Alam SM et al. Antigenicity and immunogenicity of RV144 vaccine AIDSVAX clade E envelope immunogen is enhanced by a gp120 N-terminal deletion. J Virol. 2013 Feb; 87(3):1554-68.

Simian immunodeficiency virus (SIV) - a retrovirus similar to HIV that infects African non-human primates and causes simian AIDS (SAIDS) in certain types of primates.

Simian/Human Immunodeficiency Virus (SHIV) - a genetically engineered virus with an HIV envelope and an SIV core.

Single Genome Amplification (SGA) - A PCR technique in which the template is a single genome to prevent in vitro recombination. This technique ensures the amplified DNA genomes accurately represent the diversity in vivo and are not PCR artifacts.

Structure-based B Cell Mosaic Vaccine Design - a vaccine strategy that was developed by Dr. Bette Korber at Los Alamos National Laboratory to utilize an in silico design of Envs that is based on the recombination of the regions of Env trimer neutralizing epitopes.

T Cell Mosaic Vaccine Design - a vaccine strategy that was developed by Dr. Bette Korber at Los Alamos National Laboratory to utilize an in silico design of CD8 and CD4-stimulating vaccines that is based on the recombination of T cell epitopes to minimize HIV-1 diversity.

Transmitted/founder virus - a single transmitted virus that results in HIV-1 infection.

Unmutated common ancestor antibody - an antibody that is derived either experimentally or computationally, which represents the unmutated B cell receptor of the naïve B cell from which mutated antibodies are derived.

Viral vector - a virus that has been modified to be safe for use in humans that can carry, or express, HIV genes. Viral vectors, such as pox virus vectors, are being tested as vaccine candidates.