Durability of ChAdOx1 nCov-19 (AZD1222) vaccination in people living with HIV - responses to SARS-CoV-2, variants of concern and circulating coronaviruses

Duration of protection from SARS-CoV-2 infection in people with HIV (PWH) following vaccination is unclear. In a sub-study of the phase 2/3 the COV002 trial (NCT04400838), 54 HIV positive male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells >350 cells/ul) received two doses of ChAdOx1 nCoV-19 (AZD1222) 4-6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and MesoScale Discovery (MSD)), neutralisation, ACE-2 inhibition, gamma interferon ELISpot, activation-induced marker (AIM) assay and T cell proliferation. We show that 6 months after vaccination the majority of measurable immune responses were greater than pre-vaccination baseline, but with evidence of a decline in both humoral and cell mediated immunity. There was, however, no significant difference compared to a cohort of HIV-uninfected individuals vaccinated with the same regimen. Responses to the variants of concern were detectable, although were lower than wild type. Pre-existing cross-reactive T cell responses to SARS-CoV-2 spike were associated with greater post-vaccine immunity and correlated with prior exposure to beta coronaviruses. These data support the on-going policy to vaccinate PWH against SARS-CoV-2, and underpin the need for long-term monitoring of responses after vaccination.

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Soluble Spike DNA Vaccine Provides Long-Term Protective Immunity against SARS-CoV-2 in Mice and Nonhuman Primates

Vaccines ◽

10.3390/vaccines9040307 ◽

2021 ◽

Vol 9 (4) ◽

pp. 307

Author(s):

Yong Bok Seo ◽

You Suk Suh ◽

Ji In Ryu ◽

Hwanhee Jang ◽

Hanseul Oh ◽

...

Keyword(s):

T Cell ◽

Nonhuman Primates ◽

Vaccine Candidate ◽

T Cell Responses ◽

Neutralizing Antibody ◽

Dependent Manner ◽

Viral Loads ◽

Cell Responses ◽

Rapid Spread

The unprecedented and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19-vaccinated nonhuman primates seroconverted rapidly and exhibited a detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they had reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides a durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2.

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Soluble Spike DNA vaccine provides long-term protective immunity against SAR-CoV-2 in mice and nonhuman primates

10.1101/2020.10.09.334136 ◽

2020 ◽

Author(s):

Yong Bok Seo ◽

You Suk Suh ◽

Ji In Ryu ◽

Hwanhee Jang ◽

Hanseul Oh ◽

...

Keyword(s):

T Cell ◽

Nonhuman Primates ◽

Vaccine Candidate ◽

T Cell Responses ◽

Neutralizing Antibody ◽

Dependent Manner ◽

Viral Loads ◽

Cell Responses ◽

Rapid Spread

SummaryThe unprecedented and rapid spread of SARS-CoV-2 has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19 vaccinated nonhuman primate seroconverted rapidly and exhibited detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they did not develop fever and reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2 in human clinical trials.

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Long-term virological effectiveness with darunavir/ritonavir-based salvage therapy in people living with HIV/AIDS from São Paulo, Brazil

International Journal of STD & AIDS ◽

10.1177/0956462420933716 ◽

2020 ◽

Vol 31 (10) ◽

pp. 967-975

Author(s):

Ariane Melaré Ramos dos Santos ◽

Amaury Pachione Martins ◽

Denise Juliato ◽

Érique José Farias Peixoto de Miranda ◽

Giselle Ibette Silva Lopez Lopes ◽

...

Keyword(s):

T Cell ◽

Cell Count ◽

Salvage Therapy ◽

Sao Paulo ◽

Poor Adherence ◽

Cd4 T Cell ◽

People Living With Hiv ◽

Living With Hiv ◽

Cd4 T Cell Count

Even though darunavir/ritonavir (DRV/r) has high potency and a greater genetic barrier, there are few studies on the long-term effectiveness of DRV/r-based salvage therapy in people living with HIV (PLWH) in low and middle-income countries. This retrospective cohort study, from São Paulo, Brazil, included ART-experienced PLWH aged ≥18 years with virological failure (VF) who had started DRV/r plus an optimized background regimen (OBR) between 2008 and 2012. The proportion of patients with viral load (VL) <50 copies/mL, the improved mean CD4+ T cell count and the factors associated with VF during the 144-week follow-up were assessed. The study included 173 patients with the following characteristics [median (interquartile range)]: age 48 (42 -53) years; CD4+ T cell count, 229 (89 -376) cells/mm3; VL, 4.26 (3.70 -4.74) log10; 6 (4 -7) previous regimens; and 100 (38 -156) months of VF. After 144 weeks, 129 (75%) patients had VL< 50 copies/mL and a mean increase in the CD4+ T cell count of 190 cells/mm3. VL>100,000 copies/mL and poor adherence were associated with VF. DRV/r plus an OBR showed high long-term virological suppression and immunological recovery. VL>100,000 copies/mL and poor adherence were associated with VF at 144 weeks.

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Low Immune Activation despite High Levels of Pathogenic Human Immunodeficiency Virus Type 1 Results in Long-Term Asymptomatic Disease

Journal of Virology ◽

10.1128/jvi.02663-06 ◽

2007 ◽

Vol 81 (16) ◽

pp. 8838-8842 ◽

Cited By ~ 71

Author(s):

Shailesh K. Choudhary ◽

Nienke Vrisekoop ◽

Christine A. Jansen ◽

Sigrid A. Otto ◽

Hanneke Schuitemaker ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Viral Load ◽

T Cell ◽

Immune Activation ◽

T Cell Responses ◽

Viral Loads ◽

Cell Responses ◽

Immunodeficiency Virus

ABSTRACT Long-term asymptomatic human immunodeficiency virus (HIV)-infected individuals (LTA) usually have low viral load and low immune activation. To discern whether viral load or immune activation is dominant in determining progression to AIDS, we studied three exceptional LTA with high viral loads. HIV type 1 isolates from these LTA were as pathogenic as viruses from progressors in organ culture. Despite high viral loads, these LTA had low levels of proliferating and activated T cells compared to progressors, like other LTA. In contrast to those in progressors, HIV-specific CD4+ T-cell responses in these LTA were maintained. Thus, low immune activation despite a high viral load preserved HIV-specific T-cell responses and resulted in a long-term asymptomatic phenotype.

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Cytomegalovirus-Specific CD4+ T-cell Responses and CMV-IgG Levels Are Associated With Neurocognitive Impairment in People Living With HIV

JAIDS Journal of Acquired Immune Deficiency Syndromes ◽

10.1097/qai.0000000000001753 ◽

2018 ◽

Vol 79 (1) ◽

pp. 117-125

Author(s):

Vibe Ballegaard ◽

Karin Kaereby Pedersen ◽

Maria Pedersen ◽

Peter Brændstrup ◽

Nikolai Kirkby ◽

...

Keyword(s):

T Cell ◽

T Cell Responses ◽

Neurocognitive Impairment ◽

Cd4 T Cell ◽

People Living With Hiv ◽

Cell Responses ◽

Living With Hiv

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Inactivated SARS-CoV-2 Vaccines Elicit Immunogenicity and T-cell Responses in People Living with HIV

International Immunopharmacology ◽

10.1016/j.intimp.2021.108383 ◽

2021 ◽

pp. 108383

Author(s):

Zhengchao Lv ◽

Qin Li ◽

Zaixiong Feng ◽

Xi Zheng ◽

NaYin ◽

...

Keyword(s):

T Cell ◽

T Cell Responses ◽

People Living With Hiv ◽

Cell Responses ◽

Living With Hiv

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Characterization of humoral and SARS-CoV-2 specific T cell responses in people living with HIV

10.1101/2021.02.15.431215 ◽

2021 ◽

Author(s):

Aljawharah Alrubayyi ◽

Ester Gea-Mallorquí ◽

Emma Touizer ◽

Dan Hameiri-Bowen ◽

Jakub Kopycinski ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Immune Responses ◽

T Cell Responses ◽

Mitigation Strategies ◽

Integrated Analysis ◽

People Living With Hiv ◽

Cell Responses ◽

Living With Hiv ◽

Hiv Negative

AbstractThere is an urgent need to understand the nature of immune responses generated against SARS-CoV-2, to better inform risk-mitigation strategies for people living with HIV (PLWH). Although not all PLWH are considered immunosuppressed, residual cellular immune deficiency and ongoing inflammation could influence COVID-19 disease severity, the evolution and durability of protective memory responses. Here, we performed an integrated analysis, characterizing the nature, breadth and magnitude of SARS-CoV-2-specific immune responses in PLWH, controlled on ART, and HIV negative subjects. Both groups were in the convalescent phase of predominately mild COVID-19 disease. The majority of PLWH mounted SARS-CoV-2 Spike- and Nucleoprotein-specific antibodies with neutralizing activity and SARS-CoV-2-specific T cell responses, as measured by ELISpot, at levels comparable to HIV negative subjects. T cell responses against Spike, Membrane and Nucleocapsid were the most prominent, with SARS-CoV-2-specific CD4 T cells outnumbering CD8 T cells. Notably, the overall magnitude of SARS-CoV-2-specific T cell responses related to the size of the naive CD4 T cell pool and the CD4:CD8 ratio in PLWH, in whom disparate antibody and T cell responses were observed. Both humoral and cellular responses to SARS-CoV-2 were detected at 5-7 months post-infection, providing evidence of medium-term durability of responses irrespective of HIV serostatus. Incomplete immune reconstitution on ART and a low CD4:CD8 ratio could, however, hamper the development of immunity to SARS-CoV-2 and serve as a useful tool for risk stratification of PLWH. These findings have implications for the individual management and potential effectiveness of vaccination against SARS-CoV-2 in PLWH.One Sentence SummaryAdaptive immune responses to SARS-CoV-2 in the setting of HIV infection

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Adjunct Therapy for CD4+ T-Cell Recovery, Inflammation and Immune Activation in People Living With HIV: A Systematic Review and Meta-Analysis

Frontiers in Immunology ◽

10.3389/fimmu.2021.632119 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yang Zhang ◽

Taiyi Jiang ◽

Aixin Li ◽

Zhen Li ◽

Jianhua Hou ◽

...

Keyword(s):

Systematic Review ◽

T Cell ◽

Cell Count ◽

Immune Activation ◽

Meta Analysis ◽

People Living With Hiv ◽

Cell Recovery ◽

Cell Counts ◽

Living With Hiv

Background: HIV infection results in immune homeostasis perturbations, which is characterized by CD4+ T-cell depletion, immune activation, and inflammation. Effective antiretroviral therapy (ART) does not fully restore immunologic and clinical health in people living with HIV (PLWH). Various drugs have been used to improve their immune status and CD4+ T-cell counts, but no measures have been tested effective. Here we conduct a systematic review and meta-analysis of existing clinical studies on improving CD4+ T-cell count while decreasing inflammation and immune activation.Methods: We retrieved possible relevant publications from a total of five electronic databases and selected eligible studies, which dealt with outcomes of medical therapy for CD4+ T-cell count recovery, inflammation, and immune activation with or without ART. We paid particular attention to immunologic non-responders with a favorable treatment regimen.Results: Thirty-three articles were included in the systematic review and meta-analysis. However, there were no safe and effective medications specific for improving CD4+ T-cell reconstitution. The immunological benefits or adverse events mainly depend on the safety, dosage, and duration of the candidate medication use, as well as whether it is combined with ART.Conclusion: Under the “safe, combined, adequate and long (SCAL)” principles, alternative approaches are needed to accelerate the recovery of CD4+ T-cells, and to prevent adverse long-term outcomes in PLWH with standard ART treatment.

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Expression of Inflammatory Markers RANK, MMP-9 and PTHrP in Chronic Apical Periodontitis from People Living with HIV Undergoing Antiretroviral Therapy

Journal of Clinical Medicine ◽

10.3390/jcm9113611 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3611

Author(s):

Marcio Francisco Pereira ◽

Fabio Ramoa Pires ◽

Luciana Armada ◽

Dennis Carvalho Ferreira ◽

Florence Carrouel ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Inflammatory Markers ◽

Apical Periodontitis ◽

Histopathological Diagnosis ◽

People Living With Hiv ◽

Viral Loads ◽

Parathyroid Hormone Related Protein ◽

Rank Matrix ◽

Significant Difference ◽

Living With Hiv

To compare the expression of the receptor activator of nuclear factor-kappa B (RANK), matrix metalloproteinase 9 (MMP-9) and parathyroid hormone-related protein (PTHrP) in primary chronic apical periodontitis lesions (CAPLs) between people living with HIV (PLWHIV) undergoing antiretroviral therapy (ART) and HIV- individuals, 32 CAPLs (16 lesions from each group) were submitted to histopathological and immunohistochemical analyses and compared between groups. The majority of the PLWHIV group had undetectable plasma viral loads (n = 13; 81.3%). The means of TCD4+ lymphocytes, exposure to HIV-1 and the time of the use of ART were 542.1 cells/mm3 (SD = 256.4), 6.3 years (SD = 2.9) and 5.0 years (SD = 2.5), respectively. Of all variables studied, only histopathological diagnosis showed a significant difference between groups (LWHIV: granuloma n = 11 (68.0%); cyst n = 5 (31.2%); HIV-: granuloma n = 15 (93.8%); cyst n = 1 (6.2%); p = 0.015). When comparing the expressions of the three inflammatory markers between the groups, no significant differences were seen. There was no difference in the expression of RANK, PTHrP and MMP-9 in primary chronic apical periodontitis lesions between PLWHIV under ART and HIV- individuals.

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