The attenuated oral poliovirus vaccine (OPV) has many properties favoring its use in polio eradication: ease of administration, efficient induction of intestinal immunity, induction of durable humoral immunity, and low cost. Despite these advantages, OPV has the disadvantage of genetic instability, resulting in rare and sporadic cases of vaccine-associated paralytic poliomyelitis (VAPP) and the emergence of genetically divergent vaccine-derived polioviruses (VDPVs). Whereas VAPP is an adverse event following exposure to OPV, VDPVs are polioviruses whose genetic properties indicate prolonged replication or transmission. Three categories of VDPVs are recognized: (1) circulating VDPVs (cVDPVs) from outbreaks in settings of low OPV coverage, (2) immunodeficiency-associated VDPVs (iVDPVs) from individuals with primary immunodeficiencies, and (3) ambiguous VDPVs (aVDPVs), which cannot be definitively assigned to either of the first 2 categories. Because most VDPVs are type 2, the World Health Organization's plans call for coordinated worldwide replacement of trivalent OPV with bivalent OPV containing poliovirus types 1 and 3.

This article summarizes the status of environmental surveillance (ES) used by the Global Polio Eradication Initiative, provides the rationale for ES, gives examples of ES methods and findings, and summarizes how these data are used to achieve poliovirus eradication. ES complements clinical acute flaccid paralysis (AFP) surveillance for possible polio cases. ES detects poliovirus circulation in environmental sewage and is used to monitor transmission in communities. If detected, the genetic sequences of polioviruses isolated from ES are compared with those of isolates from clinical cases to evaluate the relationships among viruses. To evaluate poliovirus transmission, ES programs must be developed in a manner that is sensitive, with sufficiently frequent sampling, appropriate isolation methods, and specifically targeted sampling sites in locations at highest risk for poliovirus transmission. After poliovirus ceased to be detected in human cases, ES documented the absence of endemic WPV transmission and detected imported WPV. ES provides valuable information, particularly in high-density populations where AFP surveillance is of poor quality, persistent virus circulation is suspected, or frequent virus reintroduction is perceived. Given the benefits of ES, GPEI plans to continue and expand ES as part of its strategic plan and as a supplement to AFP surveillance.

In contrast to pathogenic human immunodeficiency virus and simian immunodeficiency virus (SIV) infections, chronic SIVagm infections in African green monkeys (AGMs) are characterized by persistently low peripheral and tissue viral loads that correlate with the lack of disease observed in these animals. We report here data on the dynamics of acute SIVagm infection in AGMs that exhibit remarkable similarities with viral replication patterns observed in peripheral blood during the first 2 weeks of pathogenic SIVmac infections. Plasma viremia was evident at day 3 postinfection (p.i.) in AGMs, and rapid viral replication led by days 7 to 10 to peak viremias characterized by high levels of antigenemia (1.2 to 5 ng of p27/ml of plasma), peripheral DNA viral load (104 to 105 DNA copies/106 peripheral blood mononuclear cells [PBMC]), and plasma RNA viral load (2 × 106 to 2 × 108 RNA copies/ml). The lymph node (LN) RNA and DNA viral load patterns were similar to those in blood, with peaks observed between day 7 and day 14. These values in LNs (ranging from 3 × 105 to 3 × 106 RNA copies/106LN cell [LNC] and 103 to 104 DNA copies/106 LNC) were at no time point higher than those observed in the blood. Both in LNs and in blood, rapid and significant decreases were observed in all infected animals after this peak of viral replication. Within 3 to 4 weeks p.i., antigenemia was no longer detectable and peripheral viral loads decreased to values similar to those characteristic of the chronic phase of infection (102to 103 DNA copies/106 PBMC and 2 × 103 to 2 × 105 RNA copies/ml of plasma). In LNs, viral loads declined to 5 × 101 to 103 DNA copies and 104 to 3 × 105 RNA copies per 106 LNC at day 28 p.i. and continued to decrease until day 84 p.i. (<10 to 3 × 104 RNA copies/106 LNC). Despite extensive viremia during primary infection, neither follicular hyperplasia nor CD8+ cell infiltration into LN germinal centers was detected. Altogether, these results indicate that the nonpathogenic outcome of SIVagm infection in its natural host is associated with a rapidly induced control of viral replication in response to SIVagm infection, rather than with a poorly replicating virus or a constitutive host genetic resistance to virus replication.

After 8 years of silence, dengue virus serotype 2 (DENV-2) reemerged in southeastern Senegal in 1999. Sixty-four DENV-2 strains were isolated in 1999 and 9 strains in 2000 from mosquitoes captured in the forest gallery and surrounding villages. Isolates were obtained from previously described vectors, Aedes furcifer, Ae. taylori, Ae. luteocephalus, and—for the first time in Senegal—from Ae. aegypti and Ae. vittatus. A retrospective analysis of sylvatic DENV-2 outbreaks in Senegal during the last 28 years of entomologic investigations shows that amplifications are periodic, with intervening, silent intervals of 5–8 years. No correlation was found between sylvatic DENV-2 emergence and rainfall amount. For sylvatic DENV-2 vectors, rainfall seems to particularly affect virus amplification that occurs at the end of the rainy season, from October to November. Data obtained from investigation of preimaginal (i.e., nonadult) mosquitoes suggest a secondary transmission cycle involving mosquitoes other than those identified previously as vectors.

We recently developed an efficient strategy based on a fully synthetic dendrimeric carbohydrate display (multiple antigenic glycopeptide; MAG) to induce anticarbohydrate antibody responses for therapeutic vaccination against cancer. Here, we show the superior efficacy of the MAG strategy over the traditional keyhole limpet hemocyanin glycoconjugate to elicit an anticarbohydrate IgG response against the tumorassociated Tn antigen. We highlight the influence of the aglyconic carrier elements of such a tumor antigen for their recognition by the immune system. Finally, we additionally developed the MAG system by introducing promiscuous HLA-restricted T-helper epitopes and performed its immunological evaluation in nonhuman primates. MAG:Tn vaccines induced in all of the animals strong tumor-specific anti-Tn antibodies that can mediate antibody-dependent cell cytotoxicity against human tumor. Therefore, the preclinical evaluation of the MAG:Tn vaccine demonstrates that it represents a safe and highly promising immunotherapeutic molecularly defined tool for targeting breast, colon, and prostate cancers that express the carbohydrate Tn antigen.

We addressed the role of plasmacytoid dendritic cells (PDC) in protection against AIDS in nonpathogenic simian immunodeficiency virus (SIVagm) infection in African green monkeys (AGMs). PDC were monitored in blood and lymph nodes (LNs) starting from day 1 postinfection. We observed significant declines in blood during acute infection. However, PDC then returned to normal levels, and chronically infected AGMs showed no decrease of PDC in blood. There was a significant increase of PDC in LNs during acute infection. Blood PDC displayed only weak alpha interferon (IFN-␣) responses to TLR9 agonist stimulation before infection. However, during acute infection, both blood and LN PDC showed a transiently increased propensity for IFN-␣ production. Bioactive IFN-␣ was detected in plasma concomitant with the peak of viremia, though levels were only low to moderate in some animals. Plasma interleukin 6 (IL-6) and IL-12 were not increased. In conclusion, PDC were recruited to the LNs and displayed increased IFN-␣ production during acute infection. However, increases in IFN-␣ were transient. Together with the lack of inflammatory cytokine responses, these events might play an important role in the low level of T-cell activation which is associated with protection against AIDS in nonpathogenic SIVagm infection.During primary and chronic human immunodeficiency virus type 1 (HIV-1) infection, both subsets of dendritic cells (DC), i.e., myeloid dendritic cells (MDC) and plasmacytoid dendritic cells (PDC), are decreased in the blood (20,36,46). The capacity of PDC to produce IFN-␣ is impaired in acute and chronic HIV-1 infection (13,23,29). Long-term nonprogressors display higher numbers of PDC and a higher capacity for their PDC to produce IFN-␣ than progressors (46). Early profound and persistent depletions of PDC have also been observed in macaques infected with the macaque strain of simian immunodeficiency virus (SIVmac) (4, 40). Different mechanisms have been proposed to explain DC declines, including cell death and homing to lymph nodes (LNs) (4,32,40,50).Here, we investigated the dynamics and function of PDC in blood and LNs during a nonpathogenic infection, i.e., SIVagm infection in African green monkeys (AGMs). AGMs, like other African nonhuman primates, such as mandrills and mangabeys, are natural hosts for SIV and generally do not progress to AIDS despite displaying high levels of plasma and intestinal viral load (VL) (21). Natural hosts for SIV display low levels of T-cell activation, in contrast to HIV-infected humans and SIVmac-infected macaques (6). Exacerbated chronic T-cell activation might drive CD4 T-cell depletion and AIDS (19,22). An immunologic activation set point is established early after HIV-1 infection, and this set point is predictive of the rate at which CD4 ϩ T cells are lost over time (11,49). Innate immune responses acting at the early time points are crucial for T-cell activation profiles. In the present study, we studied whether PDC are recruited to LNs in response to SIVagm and analyzed early cyt...

Due to an error in manuscript preparation, an incorrect shRNA sequence for IRS2 was published. The correct hairpin sequence is a 19-nt stretch beginning from nt 703 of the published IRS2 cDNA sequence (XM_357863). The oligonucleotides cloned into the U6 construct for the IRS2U6 adenovirus are as follows: tcgagGTGACGCTGCAGCTTATGAttcaagagaTCATAAGCTGCAGCGTCACttttt (forward) and ctagAAAAAGTGACGCTGCAGCTTATGAtctcttgaaTCATAAGCTGCAGCGTCACc (reverse). In addition, the shRNA cassettes were cloned into the adenoviral cosmid pAxcwit, which lacks a promoter, and not the cosmid pAxCAwtit, as published..The authors regret this error.

To better understand which factors govern the levels of viral loads in early lentiviral infections of primates, we developed a model that allows distinguishing between the influences of host and viral factors on viremia. Herein we report that two species of African green monkeys (Chlorocebus sabaeus and C. pygerythrus) infected with their respective wild-type simian immunodeficiency virus SIVagm viruses (SIVagm.sab92018 and SIVagm. ver644) consistently showed reproducible differences in viremia during primary infection but not at later stages of infection. Cross-infections of SIVagm.sab92018 and SIVagm.ver644 into, respectively, C. pygerythrus and C. sabaeus revealed that the dynamics of viral replication during primary infection were dependent on the viral strain used for the infection but not on the host. Hence, the kinetics of SIVagm.sab92018 and SIVagm.ver644 were similar in both sabaeus and vervet animals, indicating that the difference in viremia levels between the two groups during the early phase of infection was not associated with the host. Coreceptor usage for these two strains showed a larger coreceptor repertoire for SIVagm.sab92018, which is able to efficiently use CXCR4 in addition to CCR5, than for SIVagm.ver644, which showed a classical CCR5 coreceptor usage pattern. These differences could not be explained by different charges of the V3 loop for SIVagm.sab92018 and for SIVagm. ver644. In conclusion, our study showed that the extent of virus replication during the primary infection is primarily dependent on viral determinants.