In contrast to human immunodeficiency virus (HIV)-infected humans, natural hosts for simian immunodeficiency virus (SIV) very rarely progress to acquired immunodeficiency syndrome (AIDS).While the mechanisms underlying this disease resistance are still poorly understood, a consistent feature of natural SIV infection is the absence of the generalized immune activation associated with HIV infection. To investigate the immunologic mechanisms underlying the absence of AIDS in SIV-infected sooty mangabeys (SMs), a natural host species, we performed a detailed analysis of the SIV-specific cellular immune responses in 110 SIV-infected SMs. We found that while SIV-specific T-cell responses are detectable in the majority of animals, their magnitude and breadth are, in fact, lower than what has been described in HIVinfected humans, both in terms of cytokine production (ie, IFN-␥, TNF-␣, and IL-2) and degranulation (ie, CD107a expression). Of importance, SIV-specific Tcell responses were similarly low when either SIVmac239-derived peptides or autologous SIVsmm peptides were used as stimuli. No correlation was found between SIV-specific T-cell responses and either viral load or CD4 ؉ T-cell count, or between these responses and markers of T-cell activation and proliferation. These findings indicate that the absence of AIDS in naturally SIV-infected sooty mangabeys is independent of a strong cellular immune response to the virus. IntroductionThe acquired immunodeficiency syndrome (AIDS) pandemic originated from zoonotic transmission of simian immunodeficiency viruses (SIVs) from infected African monkey species to humans. 1 Of the natural SIV hosts, sooty mangabeys (Cercocebus atys, SMs) are of interest for 2 main reasons. First, SIVsmm, the virus infecting SMs, is the origin of the human immunodeficiency virus 2 (HIV-2) epidemic in humans. 1-3 Second, SIVsmm is the source of the prototype SIVmac strains (ie, SIVmac239, SIVmac251) that induce an AIDS-like disease in the rhesus macaque (RM), a nonnatural host for SIV, and consequently are widely used for studies of AIDS pathogenesis and vaccines. 2,4-6 SIVsmm and HIV-1/2 share many features in terms of life cycle and molecular structure, and the extent of virus replication is similarly high in naturally SIV-infected SMs and HIV-infected humans. 7-9 However, the outcome of these infections is strikingly different. The vast majority of HIV-infected humans, unless treated chronically with antiretroviral therapy (ART), will develop progressive CD4 ϩ T-cell depletion and eventually succumb to AIDS. In contrast, the vast majority of naturally SIV-infected SMs maintain normal CD4 ϩ T-cell counts and live an apparently normal lifespan in captivity, [7][8][9] with only one report of classic AIDS to date. 10 It is important to note that the disease resistance of naturally SIV-infected SMs that show high levels of SIV viremia is substantially different from that of a rare subset of HIV-infected individuals defined as long-term nonprogressors, in whom viral replication is usually very lo...
The importance of vaccination during pregnancy lies not only in directly protecting vaccinated women, but also by indirectly protecting small infants during the first few months of life. Vaccination against the flu and whooping cough is a priority within the comprehensive care strategy for pregnant women and small infants in Argentina, in the context of transitioning from child vaccination to family vaccination. In 2011, the flu vaccine was included in the National Immunization Schedule (NIS) as mandatory and free of charge, with the aim of decreasing complications and death due to influenza in the at-risk population in Argentina. The national vaccination coverage attained in pregnant women in the past 4 years (2011-2014) has been satisfactory; 88% coverage was attained in the year this program was introduced to the schedule. In the following years, coverage was maintained at greater than 95%. In February 2012, Argentina became the first country in Latin America to have universal vaccination strategy for pregnant women against whooping cough. This recommendation was implemented throughout the country by vaccination with the diphtheria toxoid, tetanus toxoid, and acellular pertussis (Tdap) vaccine starting at 20 weeks of pregnancy, with the aim of decreasing morbimortality due to whooping cough in infants under 6 months of age. The vaccine was incorporated into the NIS in 2014. More than 1,200,000 doses were applied in this period. Both vaccines showed a suitable safety profile and no serious events were reported. Argentina is an example of a middle-income country that has been able to implement a successful strategy for primary prevention through vaccines, making it a health policy.
We report in vitro characterization of 11 SIVsmm strains of six lineages co-circulating in naturally infected sooty mangabeys (SMs) from US Primate Centers and showed no major differences in the in vitro replication pattern between different SIVsmm lineages. Primary SIVsmm isolates utilized CCR5 and Bonzo co-receptors in vitro. SIVsmm growth in human T cell lines was isolate-, not lineage-specific, with poor replication on Molt4-Clone8, CEMss and PM1 cells and better replication on MT2, SupT1 and CEMx174 cells. All primary SIVsmm isolates replicated on SM and human PBMCs. In vitro replication in macaques varied widely, with moderate to high replication in pig-tailed macaque PBMCs, enhanced by CD8+ T cell depletion, and highly variable replication on rhesus macaque (Rh) PBMCs. Primary SIVsmm isolates replicated in Rh monocyte-derived dendritic cells (MDDCs) and monocyte-derived macrophages (MDMs). In vivo, SIVsmm isolates replicated at high levels in all SIVsmm-infected Rh. The poor in vitro replication of primary SIVsmm isolates in Rh cells did not correlate with in vivo replication, emphasizing the value of in vivo studies.
BackgroundIn 2013, the Pan American Health Organization established a multi-site, multi-country network to evaluate influenza vaccine effectiveness (VE). We pooled data from five consecutive seasons in five countries to conduct an analysis of southern hemisphere VE against laboratory-confirmed influenza hospitalizations in young children and older adults.MethodsWe used a test-negative design to estimate VE against laboratory-confirmed influenza in hospitalized young children (aged 6─24 months) and older adults (aged ≥60 years) in Argentina, Brazil, Chile, Colombia, and Paraguay. Following country-specific influenza surveillance protocol, hospitalized persons with severe acute respiratory infections (SARI) at 48 sentinel hospitals (March 2013–December 2017) were tested for influenza virus infection by rRT-PCR. VE was estimated for young children and older adults using logistic random effects models accounting for cluster (country), adjusting for sex, age (months for children, and age-in-year categories for adults), calendar year, country, preexisting conditions, month of illness onset and prior vaccination as an effect modifier for the analysis in adults.ResultsWe included 8426 SARI cases (2389 children and 6037 adults) in the VE analyses. Among young children, VE against SARI hospitalization associated with any influenza virus was 43% (95%CI: 33%, 51%) for children who received two doses, but was 20% (95%CI: −16%, 45%) and not statistically significant for those who received one dose in a given season. Among older adults, overall VE against SARI hospitalization associated with any influenza virus was 41% (95%CI: 28%, 52%), 45% (95%CI: 34%, 53%) against A(H3N2), 40% (95%CI: 18%, 56%) against A(H1N1)pdm09, and 20% (95%CI: −40%, 54%) against influenza B viruses.ConclusionsOur results suggest that over the five-year study period, influenza vaccination programs in five South American countries prevented more than one-third of laboratory confirmed influenza-associated hospitalizations in young children receiving the recommended two doses and vaccinated older adults.
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