The Antibody Response against HIV-1

Overbaugh, Julie; Morris, Lynn

doi:10.1101/cshperspect.a007039

Cited by 156 publications

(119 citation statements)

References 151 publications

Supporting

Mentioning

113

Contrasting

Unclassified

Order By: Relevance

“…Neutralization responses have inconsistently been associated with reduced prenatal, perinatal, or postnatal mother-to-child HIV-1 transmission risk, and prior studies differ in study design, cohort size, prevalent virus clade, use of autologous or heterologous HIV-1 virus strains, mode of HIV-1 transmission, and timing of sample collection (39,40).…”

Section: Discussionmentioning

confidence: 99%

Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1

Pollara

McGuire

Fouda

et al. 2015

J Virol

View full text Add to dashboard Cite

Infants born to HIV-1-infected mothers in resource-limited areas where replacement feeding is unsafe and impractical are repeatedly exposed to HIV-1 throughout breastfeeding. Despite this, the majority of infants do not contract HIV-1 postnatally, even in the absence of maternal antiretroviral therapy. This suggests that immune factors in breast milk of HIV-1-infected mothers help to limit vertical transmission. We compared the HIV-1 envelope-specific breast milk and plasma antibody responses of clade C HIV-1-infected postnatally transmitting and nontransmitting mothers in the control arm of the Malawi-based Breastfeeding Antiretrovirals and Nutrition Study using multivariable logistic regression modeling. We found no association between milk or plasma neutralization activity, antibody-dependent cell-mediated cytotoxicity, or HIV-1 envelope-specific IgG responses and postnatal transmission risk. While the envelope-specific breast milk and plasma IgA responses also did not reach significance in predicting postnatal transmission risk in the primary model after correction for multiple comparisons, subsequent exploratory analysis using two distinct assay methodologies demonstrated that the magnitudes of breast milk total and secretory IgA responses against a consensus HIV-1 envelope gp140 (B.con env03) were associated with reduced postnatal transmission risk. These results suggest a protective role for mucosal HIV-1 envelope-specific IgA responses in the context of postnatal virus transmission. This finding supports further investigations into the mechanisms by which mucosal IgA reduces risk of HIV-1 transmission via breast milk and into immune interventions aimed at enhancing this response. IMPORTANCEInfants born to HIV-1-infected mothers are repeatedly exposed to the virus in breast milk. Remarkably, the transmission rate is low, suggesting that immune factors in the breast milk of HIV-1-infected mothers help to limit transmission. We compared the antibody responses in plasma and breast milk of HIV-1-transmitting and -nontransmitting mothers to identify responses that correlated with reduced risk of postnatal HIV-1 transmission. We found that neither plasma nor breast milk IgG antibody responses were associated with risk of HIV-1 transmission. In contrast, the magnitudes of the breast milk IgA and secretory IgA responses against HIV-1 envelope proteins were associated with reduced risk of postnatal HIV-1 transmission. The results of this study support further investigations of the mechanisms by which mucosal IgA may reduce the risk of HIV-1 transmission via breastfeeding and the development of strategies to enhance milk envelope-specific IgA responses to reduce mother-to-child HIV transmission and promote an HIV-free generation.

show abstract

Section: Discussionmentioning

confidence: 99%

Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1

Pollara

McGuire

Fouda

et al. 2015

J Virol

View full text Add to dashboard Cite

show abstract

“…While exciting advances have been made toward understanding how antibodies protect against infection by many different viruses, this review focuses on the neutralizing-antibody response against members of the flavivirus genus. To identify general concepts, selected insights into the anti-HIV-1 antibody response are presented; excellent detailed reviews of the HIV-1 antibody response were reported previously (10,(13)(14)(15). Both groups of viruses have a global impact on public health and vary considerably in structure and replication strategies.…”

Section: Flaviviruses and Hiv-1: Clinically Significant Contexts For mentioning

confidence: 99%

Deconstructing the Antiviral Neutralizing-Antibody Response: Implications for Vaccine Development and Immunity

VanBlargan

Goo

Pierson

2016

Microbiol Mol Biol Rev

View full text Add to dashboard Cite

SUMMARY The antibody response plays a key role in protection against viral infections. While antiviral antibodies may reduce the viral burden via several mechanisms, the ability to directly inhibit (neutralize) infection of cells has been extensively studied. Eliciting a neutralizing-antibody response is a goal of many vaccine development programs and commonly correlates with protection from disease. Considerable insights into the mechanisms of neutralization have been gained from studies of monoclonal antibodies, yet the individual contributions and dynamics of the repertoire of circulating antibody specificities elicited by infection and vaccination are poorly understood on the functional and molecular levels. Neutralizing antibodies with the most protective functionalities may be a rare component of a polyclonal, pathogen-specific antibody response, further complicating efforts to identify the elements of a protective immune response. This review discusses advances in deconstructing polyclonal antibody responses to flavivirus infection or vaccination. Our discussions draw comparisons to HIV-1, a virus with a distinct structure and replication cycle for which the antibody response has been extensively investigated. Progress toward deconstructing and understanding the components of polyclonal antibody responses identifies new targets and challenges for vaccination strategies.

show abstract

“…1-6 and reviewed in refs. [7][8][9][10][11]. Passive immunization studies show that sterilizing immunity can be achieved if sufficient amounts of bnAbs are present before virus challenge in macaques (12)(13)(14)(15)(16).…”

mentioning

confidence: 99%

Asymmetric recognition of the HIV-1 trimer by broadly neutralizing antibody PG9

Julien

Lee

Cupo

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

230

303

View full text Add to dashboard Cite

PG9 is the founder member of an expanding family of glycandependent human antibodies that preferentially bind the HIV (HIV-1) envelope (Env) glycoprotein (gp) trimer and broadly neutralize the virus. Here, we show that a soluble SOSIP.664 gp140 trimer constructed from the Clade A BG505 sequence binds PG9 with high affinity (∼11 nM), enabling structural and biophysical characterizations of the PG9:Env trimer complex. The BG505 SOSIP.664 gp140 trimer is remarkably stable as assessed by electron microscopy (EM) and differential scanning calorimetry. EM, small angle X-ray scattering, size exclusion chromatography with inline multiangle light scattering and isothermal titration calorimetry all indicate that only a single PG9 fragment antigen-binding (Fab) binds to the Env trimer. An ∼18 Å EM reconstruction demonstrates that PG9 recognizes the trimer asymmetrically at its apex via contact with two of the three gp120 protomers, possibly contributing to its reported preference for a quaternary epitope. Molecular modeling and isothermal titration calorimetry binding experiments with an engineered PG9 mutant suggest that, in addition to the N156 and N160 glycan interactions observed in crystal structures of PG9 with a scaffolded V1/V2 domain, PG9 makes secondary interactions with an N160 glycan from an adjacent gp120 protomer in the antibody-trimer complex. Together, these structural and biophysical findings should facilitate the design of HIV-1 immunogens that possess all elements of the quaternary PG9 epitope required to induce broadly neutralizing antibodies against this region. R ational immunogen design is an increasingly promising approach for development of an effective human immunodeficiency virus-1 (HIV-1) vaccine. The recent discovery of many new and potent broadly neutralizing antibodies (bnAbs) has helped define conserved sites of vulnerability on the HIV-1 envelope (Env) glycoprotein (gp) complex that mediates viral entry into cells (refs. 1-6 and reviewed in refs. 7-11). Passive immunization studies show that sterilizing immunity can be achieved if sufficient amounts of bnAbs are present before virus challenge in macaques (12-16). Hence, intensive efforts are ongoing to design immunogens capable of re-eliciting these types of bnAbs by vaccination.The major difficulty in mounting an effective antibody response against HIV-1 resides in the multiple evasion strategies that have evolved in Env. An error-prone reverse transcriptase drives a high degree of Env sequence diversity (17-19). The few conserved regions of Env are shielded by an extensive array of glycans (20-24) and are often occluded by more variable structures, such as the V1-V5 loops. However, because some HIV-1-infected individuals can develop bnAbs over the course of infection, these various evasion strategies are not insurmountable (1,(25)(26)(27). Although bnAbs do not seem to confer significant protection against disease progression in infected individuals (28, 29), their induction through vaccination might prevent the acquisition of infection. ...

show abstract

The Antibody Response against HIV-1

Cited by 156 publications

References 151 publications

Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1

Association of HIV-1 Envelope-Specific Breast Milk IgA Responses with Reduced Risk of Postnatal Mother-to-Child Transmission of HIV-1

Deconstructing the Antiviral Neutralizing-Antibody Response: Implications for Vaccine Development and Immunity

Asymmetric recognition of the HIV-1 trimer by broadly neutralizing antibody PG9

Contact Info

Product

Resources

About