Antibody Responses to HIV-1 Envelope and GAG Epitopes in HIV-1 Seroconverters with Rapid versus Slow Disease Progression

Zwart, G.; Hoek, Lia van der; Valk, M. van der; Cornelissen, Marion; Baan, Elly; Dekker, Joseph D.; Koot, M.; Kuiken, Carla; Goudsmit, Jaap

doi:10.1006/viro.1994.1293

Cited by 51 publications

(38 citation statements)

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“…That the viral load did not decrease after the earlier viremia peak in the rapid progressors strongly suggests that these infants were not able to control viral replication, as usually occurs in adults after the primary infection (30)(31). The presence of autochthonous antibodies binding to several HIV-1 gag and envelope epitopes, could be documented in 3 out of 4 rapid progressors, and 4 out of 5 slow progressors early in life (8; and unpublished results); therefore, in agreement with other studies (32,33), such antibodies did not appear to play a critical role in determining the pattern of infection. As viral decline after primary infection in adults has mainly been associated with the emergence of HIV-1 specific cytotoxic T lymphocytes (CTL) (34)(35)(36), the viral decline observed in slow progressors might indicate that these infants were able to mount a cellular immune response, and partially control HIV-1 replication.…”

Section: Discussionsupporting

confidence: 88%

Dynamics of viral replication in infants with vertically acquired human immunodeficiency virus type 1 infection.

Rossi¹,

Masiero²,

Giaquinto³

et al. 1996

J. Clin. Invest.

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About one-third of vertically HIV-1 infected infants develop AIDS within the first months of life; the remainder show slower disease progression. We investigated the relationship between the pattern of HIV-1 replication early in life and disease outcome in eleven infected infants sequentially studied from birth. Viral load in cells and plasma was measured by highly sensitive competitive PCR-based methods.Although all infants showed an increase in the indices of viral replication within their first weeks of life, three distinct patterns emerged: ( a ) a rapid increase in plasma viral RNA and cell-associated proviral DNA during the first 4-6 wk, reaching high steady state levels ( Ͼ 1,000 HIV-1 copies/10 5 PBMC and Ͼ 1,000,000 RNA copies/ml plasma) within 2-3 mo of age; ( b ) a similar initial rapid increase in viral load, followed by a 2.5-50-fold decline in viral levels; ( c ) a significantly lower ( Ͼ 10-fold) viral increase during the first 4-6 wk of age. All infants displaying the first pattern developed early AIDS, while infants with slower clinical progression exhibited the second or third pattern.These findings demonstrate that the pattern of viral replication and clearance in the first 2-3 mo of life is strictly correlated with, and predictive of disease evolution in vertically infected infants. ( J. Clin. Invest. 1996. 97:323-330.)

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Section: Discussionsupporting

confidence: 88%

Dynamics of viral replication in infants with vertically acquired human immunodeficiency virus type 1 infection.

Rossi¹,

Masiero²,

Giaquinto³

et al. 1996

J. Clin. Invest.

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show abstract

“…Although studies with a larger patient cohort are required for confirmation, our preliminary data suggest that IgG against this epitope does not contribute significantly to protection against primary WNV infection. This is similar is to what has been observed in human immunodeficiency virus infections, where the level or type of antibodies does not predict disease progression (53,61). Alternatively, serum sampling 4 to 6 months after infection may give an incomplete picture of the function of particular antibodies at a given stage of disease.…”

Section: Discussionsupporting

confidence: 74%

Induction of Epitope-Specific Neutralizing Antibodies against West Nile Virus

Oliphant¹,

Nybakken

Austin

et al. 2007

J Virol

161

199

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Previous studies have established that an epitope on the lateral ridge of domain III (DIII-lr) of West Nile virus (WNV) envelope (E) protein is recognized by strongly neutralizing type-specific antibodies. In contrast, an epitope against the fusion loop in domain II (DII-fl) is recognized by flavivirus cross-reactive antibodies with less neutralizing potential. Using gain-and loss-of-function E proteins and wild-type and variant WNV reporter virus particles, we evaluated the expression pattern and activity of antibodies against the DIII-lr and DII-fl epitopes in mouse and human serum after WNV infection. In mice, immunoglobulin M (IgM) antibodies to the DIII-lr epitope were detected at low levels at day 6 after infection. However, compared to IgG responses against other epitopes in DI and DII, which were readily detected at day 8, the development of IgG against DIII-lr epitope was delayed and did not appear consistently until day 15. This late time point is notable since almost all death after WNV infection in mice occurs by day 12. Nonetheless, at later time points, DIII-lr antibodies accumulated and comprised a significant fraction of the DIII-specific IgG response. In sera from infected humans, DIII-lr antibodies were detected at low levels and did not correlate with clinical outcome. In contrast, antibodies to the DII-fl were detected in all human serum samples and encompassed a significant percentage of the anti-E protein response. Our experiments suggest that the highly neutralizing DIII-lr IgG antibodies have little significant role in primary infection and that the antibody response of humans may be skewed toward the induction of cross-reactive, less-neutralizing antibodies.

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“…Reactivities with specific epitopes on gp120 have been associated with good or bad disease prognosis, but the potency of the predictive value of these responses remains unclear. [23][24][25][36][37][38] Here we show that high pre-existing gp120 binding antibody titers were a strong negative correlate of immune functions and viremia control. This may seem paradoxical because anti-Env antibodies can harbor inhibitory activity and, thus, high titers of these antibodies should be of benefit.…”

Section: Discussionmentioning

confidence: 99%

Humoral immunity to HIV-1: kinetics of antibody responses in chronic infection reflects capacity of immune system to improve viral set point

Trkola¹

2004

Blood

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We analyzed the humoral immune response in 46 patients following structured treatment interruption (STI) to investigate the general potential of therapeutic vaccination in chronic HIV-1 infection. Evoked antibody titer increases to glycoprotein 120 (gp120) and p24 were low during 4 short-term STIs and only reached significance during a fifth long-term interruption. Although induction of binding antibodies to viral antigens was not associated with potent suppression of viremia, we observed that individuals with a rapid and high response to p24, and to a lesser extent also to gp120, lowered their viral set points significantly. Of note, the increase of the anti-p24 response correlated with specific CD4 T helper frequency to this antigen. Despite induction of binding antibody responses, which correlated with improved viral control, the increase in neutralizing activity was marginal and did not lead to this enhanced viral suppression. However, a subgroup of patients who potently suppressed viremia independently of STI had significantly higher pre-existing neutralization titers, suggesting a role of humoral immunity in conferring potent protection. In summary, measuring the kinetics of antibody responses provided a marker to validate the responsiveness and capacities of the immune system of HIV-1-infected individuals and reflected the patients' ability to decrease viral set points.

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Antibody Responses to HIV-1 Envelope and GAG Epitopes in HIV-1 Seroconverters with Rapid versus Slow Disease Progression

Cited by 51 publications

References 0 publications

Dynamics of viral replication in infants with vertically acquired human immunodeficiency virus type 1 infection.

Dynamics of viral replication in infants with vertically acquired human immunodeficiency virus type 1 infection.

Induction of Epitope-Specific Neutralizing Antibodies against West Nile Virus

Humoral immunity to HIV-1: kinetics of antibody responses in chronic infection reflects capacity of immune system to improve viral set point

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