Unexpectedly higher levels of anti-orthopoxvirus neutralizing antibodies are observed among gay men than general adult population.

BACKGROUND: The confirmed cases in the current outbreak of Monkeypox are predominantly identified in the networks of men who have sex with men (MSM). The preexisting antibodies may profoundly impact the transmission of monkeypox virus (MPXV), however the current-day prevalence of antibodies against MPXV among gay men is not well characterized. METHODS: A cohort of gay men (n = 326) and a cohort of the general adult population (n = 295) were enrolled in this study. Binding antibodies responses against MPXV/vaccinia and neutralizing antibody responses against vaccinia virus (Tiantan strain) were measured. The antibody responses of these two cohorts were then compared, as well as the responses of individuals born before and in/after 1981 (when the smallpox vaccination ceased in China). Finally, the correlation between the anti-MPXV antibody responses and the anti-vaccinia antibody responses, and the associations between preexisting anti-orthopoxvirus antibody responses and the diagnosed sexually transmitted infections (STIs) in the MSM cohort were analyzed separately. RESULTS: Our data showed that binding antibodies against MPXV H3, A29, A35, E8, B6, M1 proteins and vaccinia whole-virus lysate could be detected in individuals born both before and in/after 1981, of which the prevalence of anti-vaccinia binding antibodies was significantly higher among individuals born before 1981 in the general population cohort. Moreover, we unexpectedly found that the positive rates of binding antibody responses against MPXV H3, A29, A35, E8 and M1 proteins were significantly lower among individuals of the MSM cohort born in/after 1981, but the positive rates of anti-MPXV B6 and anti-vaccinia neutralizing antibody responses were significantly higher among these individuals compared to those of age-matched participants in the general population cohort. Additionally, we demonstrated that the positive and negative rates of anti-MPXV antibody responses were associated with the anti-vaccinia antibody responses among individuals born before 1981 in the general population cohort, but no significant association was observed among individuals born in/after 1981 in both cohorts. The positive rates of both the binding and the neutralizing antibody responses were comparable between individuals with and without diagnosed STIs in the MSM cohort. CONCLUSIONS: Anti-MPXV and anti-vaccinia antibodies could be readily detected in an MSM cohort and a general population cohort. And a higher level of anti-vaccinia neutralizing antibody responses was observed among individuals who did not get vaccinated against smallpox in the MSM cohort compared to age-matched individuals in the general population cohort.

Immunogenicity of an inactivated SARS-CoV-2 vaccine in people living with HIV-1: a non-randomized cohort study.

BACKGROUND: Inactivated COVID-19 vaccines are safe and effective in the general population with intact immunity. However, their safety and immunogenicity have not been demonstrated in people living with HIV (PLWH). METHODS: 42 HIV-1 infected individuals who were stable on combination antiretroviral therapy (cART) and 28 healthy individuals were enrolled in this open-label two-arm non-randomized study at Hubei Provincial Center for Disease Control and Prevention, China. Two doses of an inactivated COVID-19 vaccine (BBIBP-CorV) were given on April 22, 2021 and May 25, 2021, respectively. The reactogenicity of the vaccine were evaluated by observing clinical adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and surrogate neutralization assays. Cell-mediated immune responses and vaccine induced T cell activation were measured by flow cytometry. FINDINGS: All the HIV-1 infected participants had a CD4+ T cell count >200 cells/µL both at baseline (659·0 ± 221·9 cells/µL) and 4 weeks after vaccination (476·9 ± 150·8 cells/µL). No solicited adverse reaction was observed among all participants. Similar binding antibody, neutralizing antibody and S protein specific T cell responses were elicited in PLWH and healthy individuals. PLWH with low baseline CD4+/CD8+ T cell ratios (<0·6) generated lower antibody responses after vaccination than PLWH with medium (0·6∼1·0) or high (≥1·0) baseline CD4+/CD8+ T cell ratios (P<0·01). The CD3+, CD4+ and CD8+ T cell counts of PLWH decreased significantly after vaccination (P<0·0001), but it did not lead to any adverse clinical manifestation. Moreover, we found that the general HIV-1 viral load among the PLWH cohort decreased significantly after vaccination (P=0·0192). The alteration of HIV-1 viral load was not significantly associated with the vaccine induced CD4+ T cell activation (P>0·2). INTERPRETATION: Our data demonstrated that the inactivated SARS-CoV-2 vaccine was safe, immunogenic in PLWH who are stable on cART with suppressed viral load and CD4+ T cell count > 200 cells/µL. However, the persistence of the vaccine-induced immunities in PLWH need to be further investigated.

Short Communication: The Distribution of Potential N-Linked Glycosylation Sites in Gp120 Differs Among Major HIV-1 Subtypes Circulating in China.

CRF01_AE shows an obvious sexual transmission advantage over other major HIV-1 subtypes circulating in China. Previous studies showed that the presence or absence of potential N-linked glycosylation sites (PNGSs) in variable loops might affect HIV-1 transmission; it is therefore of interest to compare the distribution of potential PNGSs on envelopes of different subtypes circulating in China. Compared to CRF07_BC, CRF08_BC, B, and B' subtypes isolated in China, CRF01_AE subtypes isolated from both China and outside China had significantly fewer PNGSs in total and in V2/V4, while they had significantly more PNGSs in V5. HIV-1 subtype CRF01_AE has a unique PNGS distribution pattern in Gp120, which may contribute to its advantage in sexual transmission in China.

[Analysis of characteristics and therapy of clients in the extension methadone maintenance therapy clinic].

OBJECTIVE: To understand the characteristics and retention situation of clients in extension clinic of methadone maintenance therapy. METHODS: From December 20, 2010 to March 10, 2011, the system sampling method was used to get the cases. A total of 462 heroin addicts from 22 methadone maintenance therapy clinics and extension clinics located in Mangshi, Ruili, Longchuan, Yingjiang, Lianghe of Dehong prefecture, Yunnan province were interviewed, and the demographic characteristics, quality of life, urine testing results for morphine of the patients between the extension MMT clinic and standard MMT clinic were also collected and compared. A cohort study was conducted to analyze retention situation of the new clients with Kaplan Meier method during 9 months treatment. RESULTS: Of the 462 cases, 239 cases were from standard MMT clinic, and 223 cases were from the extension MMT clinic. Among them, 117 cases were new research objects into the group during the investigation. Among the clients of extension MMT clinic, 96.7% (147/152) of them were males, 37.5% (57/152) were Dai nationality, and 61.2% (93/152) were married, 38.8% (59/152) with primary school education, 95.4% (145/152) lived with their family or relatives, 96.7% (147/152) could arrive at the clinic from their habitation within 15 minutes. The positive detection rates 72% (13/18), 71% (24/34), 58% (30/52), 29% (15/52), 14% (6/44), 14% (4/29), 15% (5/34), 17% (6/35), 6% (2/33), 16% (5/31) of urine-morphine testing among new clients of extension MMT clinics decreased as the period of treatment lengthened (χ(2) = 61.04, P < 0.05). The period of retention of the clients in extension MMT clinics was 175-days averagely, with an average retention 122 days of when withdrawing. The retention rates of the clients were 52% (37/71)and 61% (28/46) at 9th month of the extension MMT clinics and standard MMT clinics respectively. There was no difference in the retention rate between those of two types of clinics (χ(2) = 0.82, P = 0.37) . CONCLUSION: Most of the clients in extension MMT clinics lived with their family or relatives, and spent less time on the way to the clinics. After 9 months methadone maintenance therapy, the quality of life of clients in extension clinics was improved while addiction among them decreased. The extension clinic was an effective strategy for retention in remote areas.

Partial protection of SHIV-infected Chinese rhesus macaques against super-infection with heterologous SHIV isolate.

BACKGROUND: Many studies have revealed a protective effect of infection with simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV) against subsequent infection by a related immunodeficiency virus. However, whether a protective response can be induced by an infection with an immunodeficiency virus is still currently debated in the HIV-1 vaccine field. The aim of this study was to evaluate the protection against SHIV challenge in Chinese macaques that had been inoculated with SHIVs containing different HIV-1 envelops. METHODS: Eleven adult Chinese rhesus monkeys were inoculated with SHIV-KB9, SHIV-1157ipd3N4 or SHIV-CN97001. After 30 weeks, the animals were exposed to SHIV-KB9 or SHIV-CN97001, which carried a heterologous envelope protein relative to the first challenge strain. Infection was monitored by measuring viral load and antibody response, as well as viral genome sequence analyses. RESULTS: After first challenge, all the monkeys demonstrated high viral loads and specific antibody responses. Protection from super-infection was statistically significant in all the animals inoculated with SHIV-KB9 or SHIV-1157ipd3N4. However, animals inoculated with SHIV-CN97001 and challenged with SHIV-KB9 showed new infections. The susceptibility to super-infection was not correlated with neutralizing antibodies present at the time of exposure to the second virus. CONCLUSIONS: These findings indicate that different SHIV infection may confer different levels of protection against a second SHIV infection in Chinese monkeys. Understanding this protective response in SHIV infected macaques may shed a new light on HIV-1 vaccine development.

Infection and pathogenesis of Huaiyangshan virus (a novel tick-borne bunyavirus) in laboratory rodents.

A novel tick-borne bunyavirus (Huaiyangshan virus, HYSV), which causes haemorrhagic fever-like disease, has recently been reported in China. So far no animal experiments have been performed to study its pathogenesis. Towards developing an animal model for HYSV fever, newborn and adult mice and rats and golden hamsters were inoculated intracerebrally or intraperitoneally with HYSV. Newborn rats and newborn mice, especially Kunming (KM) mice, appeared highly susceptible. Remarkably, the KM mice that died of the HYSV infection developed large necrotic areas in the liver, while no obvious pathological changes were observed within the other organs. PCR and immunohistochemical analyses of the post-mortem material detected both HYSV antigen and RNA in almost all organs, indicating a systemic infection. Our data demonstrate that HYSV can cause a lethal infection of both newborn mice and newborn rats with apparent pathological damage of the liver. This animal model may help to understand the pathogenesis of the HYSV infection in humans.

Comparison of the quantities and subset distributions of natural killer cells among different races.

BACKGROUND: Natural killer (NK) cells play critical roles in host immune defense, while the quantities and subset distributions may vary among different races. To address the difference, we compared these variables among Chinese Han, the Caucasians and the Blacks. The study may provide critical background information for both basic research and clinical investigation. METHODS: Blood samples collected from populations of different races were tested within 12 hours after collection and subsets of NK cells were characterized using flow cytometry. RESULTS: The absolute NK count in the Chinese Han was significantly higher than that in the Caucasian. The Han and Caucasian groups showed higher percentages of cytotoxic subset compared to that of the Black group. The percentage of cytokine-producing subset of Chinese Han group was lower than that of Caucasian and Black groups. Black group had a higher percentage of function-unknown NK subset than that of the Han and Caucasian groups. CONCLUSION: Our data indicated that NK cell count and the distribution of different subsets varied among different races, which should be taken into consideration in related investigations.

HIV-specific IL-2(+) and/or IFN-γ(+) CD8(+) T cell responses during chronic HIV-1 infection in former blood donors.

OBJECTIVE: Conflicting data have been generated from previous studies to determine which kind of relationship exists between HIV-1 specific CD8 Tcell responses and HIV-1 viral load or CD4 count over the course of infection. In this study, 153 HIV-1 infected LTNPs were enrolled to investigate the role of HIV-1 specific CD8 T-cell responses in chronic HIV-1 infection among HIV-1 infected former blood donors. METHODS: The patients were stratified into three groups according to CD4 count: CD4≥500 cells/µL; 350 cells/µL≤CD4<500 cells/µL; CD4<350 cells/µL. PBMCs were isolated from the patients' anticoagulated blood samples. IL-2 and IFN-γ secretions of CD 8 T cells against 17 HIV-1 consensus B full peptide pools were analyzed by using ICS assay. RESULTS: An overall inverse correlation were observed between CD4 count and plasma viral load. Although no significant difference was observed during the comparisons of frequency/breadth of HIV-1 specific CD8 T cell responses, CD4 count stratification analysis showed that different correlation pattern existed in three strata: as for patients whose CD4 counts were less than 350 cells/µL, no significant correlations were identified between frequency/breadth of HIV-1 specific CD8 T cell responses and CD4 count/viral load; as for patients whose CD4 counts ranged from 350 cells/µL to 500 cells/µL, significant correlation was only observed between the response breadth of IL-2+IFN-γ+ CD8 T cells and CD4 count; however, as for patients whose CD4 counts were more than 500 cells/µL, direct correlations were identified between IL-2+IFN-γ+/IL-2+/IFN-γ+ CD8 T cells and viral load or CD4 count. CONCLUSIONS: Universal consistent inverse correlation was only indentified between CD4 count and viral load. The relationship between HIV-1 specific CD8 T cell responses and CD4 count/viral load varied in different CD4 strata, which showed that better preserved CD4 T cells were correlated with better CD8 T cell functions.

A mouse model based on replication-competent Tiantan vaccinia expressing luciferase/HIV-1 Gag fusion protein for the evaluation of protective efficacy of HIV vaccine.

BACKGROUND: Developing an effective vaccine against human immunodeficiency virus type 1 (HIV-1) remains a grand challenge after more than two decades of intensive effort. It is partially due to the lack of suitable animal models for screening and prioritizing vaccine candidates. In this study, we aim to develop a mice model to test HIV-1 vaccine efficacy. METHODS: We constructed a recombinant vaccinia expressing firefly luciferase and HIV-1 Gag fusion protein based on Tiantan strain, an attenuated but replication-competent poxvirus (rTTV-lucgag). By quantifying the luciferase activity as its read out, we defined the biodistribution of Tiantan strain poxvirus in mice inoculated intraperitoneally and attempted to apply this model to evaluate the HIV-1 vaccine efficacy. RESULTS: Our data demonstrated that the rTTV-lucgag was able to express high level of luciferase (< or = 10(6) relative luciferase units (RLU)/mg protein) and HIV-1 Gag (> 3 folds increase comparing to the control). After intraperitoneal inoculation, this virus had dominant replication in the ovary, uterus, and cervix of mice and the luciferase activities in those organs are significantly correlated with viral titers (r(2) = 0.71, P < 0.01). Pre-immunization with an HIV gag DNA vaccine reduced the luciferase activity in ovary from (6006 +/- 3141) RLU/mg protein in control group to (1538 +/- 463) RLU/mg protein in vaccine group (P = 0.1969). CONCLUSIONS: The luciferase activity in ovary could represent viral replication in vivo; this rTTV-lucgag/mice model may be suitable to assess the protective efficacy of cytotoxic T-cell responses to HIV Gag with less tedious work and high through-put.

[Effect of GBV-C/HIV coinfection on HIV/AIDS disease progression and HIV replication].

Several research groups have recently reported that persistent GB virus C (GBV-C) co-infected with human immunodeficiency virus (HIV) leads to slower AIDSs disease progression than HIV-1 infection alone. However, these findings were not confirmed by several other studies. To investigate the association between GBV-C replication and plasma HIV loads and CD4+ T cell counts, 203 HIV-1 positive former blood/plasma donors(FBDs) were enrolled from Fuyang city of Anhui Province in China. Plasma specimens were collected from them and were tested for GBV-C using RT-PCR and ELISA. Out of 203 specimens, 52 (25.6%) cases were positive for GBV-C, including 35 male (67.3%) and 17 female (32.7%) cases. No significant association was identified between GBV-C infection and CD4+ T-cell counts or between GBV-C infection and HIV viral loads. Since all the subjects studied were naive to ART, the influence of therapy on AIDS disease progression was ruled out in this study. Overall, our data indicated that HIV-1 positive male FBDs were prone to be infected, GBV-C coinfection with HIV-1 does not significantly influence HIV/AIDS disease progression during the late stage of chronic HIV-1 infection.