Conjugated anionic PEG-citrate G2 dendrimer with multi-epitopic HIV-1 vaccine candidate enhance the cellular immune responses in mice

Middle East respiratory syndrome (MERS) is an acute, high-mortality-rate, severe infectious disease caused by an emerging MERS coronavirus (MERS-CoV) that causes severe respiratory diseases. The continuous spread and great pandemic potential of MERS-CoV make it necessarily important to develop effective vaccines. We previously demonstrated that the application of Gram-positive enhancer matrix (GEM) particles as a bacterial vector displaying the MERS-CoV receptor-binding domain (RBD) is a very promising MERS vaccine candidate that is capable of producing potential neutralization antibodies. We have also used the rabies virus (RV) as a viral vector to design a recombinant vaccine by expressing the MERS-CoV S1 (spike) protein on the surface of the RV. In this study, we compared the immunological efficacy of the vaccine candidates in BALB/c mice in terms of the levels of humoral and cellular immune responses. The results show that the rabies virus vector-based vaccine can induce remarkably earlier antibody response and higher levels of cellular immunity than the GEM particles vector. However, the GEM particles vector-based vaccine candidate can induce remarkably higher antibody response, even at a very low dose of 1 µg. These results indicate that vaccines constructed using different vaccine vector platforms for the same pathogen have different rates and trends in humoral and cellular immune responses in the same animal model. This discovery not only provides more alternative vaccine development platforms for MERS-CoV vaccine development, but also provides a theoretical basis for our future selection of vaccine vector platforms for other specific pathogens.

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Erratum to “Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime–protein boost HIV-1 vaccine in healthy human volunteers” [Vaccine 26 (2008) 1098–1110]

Vaccine ◽

10.1016/j.vaccine.2008.04.025 ◽

2008 ◽

Vol 26 (31) ◽

pp. 3946

Keyword(s):

Immune Responses ◽

Healthy Human ◽

Cellular Immune Responses ◽

Protein Boost ◽

Human Volunteers ◽

Cellular Immune ◽

Hiv 1

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HIV-1-specific cellular immune responses among HIV-1-resistant sex workers

Immunology and Cell Biology ◽

10.1046/j.1440-1711.2000.00944.x ◽

2000 ◽

Vol 78 (6) ◽

pp. 586-595 ◽

Cited By ~ 71

Author(s):

Keith R Fowke ◽

Rupert Kaul ◽

Kenneth L Rosenthal ◽

Julius Oyugi ◽

Joshua Kimani ◽

...

Keyword(s):

Immune Responses ◽

Sex Workers ◽

Cellular Immune Responses ◽

Cellular Immune ◽

Hiv 1

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Inhibition of lipid antigen presentation in dendritic cells by HIV-1 Vpu interference with CD1d recycling from endosomal compartments

Blood ◽

10.1182/blood-2009-09-243667 ◽

2010 ◽

Vol 116 (11) ◽

pp. 1876-1884 ◽

Cited By ~ 85

Author(s):

Markus Moll ◽

Sofia K. Andersson ◽

Anna Smed-Sörensen ◽

Johan K. Sandberg

Keyword(s):

Dendritic Cells ◽

Immune Responses ◽

Antigen Presentation ◽

Nkt Cells ◽

Cellular Immune Responses ◽

Antigen Presentation Pathway ◽

Early Endosomes ◽

Presentation Pathway ◽

Cellular Immune ◽

Hiv 1

AbstractDendritic cells (DCs) play an important role in viral infections both as initiators of immunity and as viral targets. Interaction between DCs and the innate-like CD1d-restricted natural killer T (NKT) cells results in the mutual activation of both cells and the subsequent initiation of cellular immune responses. Here, we show that HIV-1 inhibits the surface expression of CD1d in productively infected DCs and identify this as a novel activity of the HIV-1 vpu gene product. Interestingly, the viral protein U (Vpu) does not enhance constitutive CD1d endocytosis or induce rapid CD1d degradation. Instead, the Vpu protein interacts with CD1d and suppresses its recycling from endosomal compartments to the cell surface by retaining CD1d in early endosomes. This interference with the CD1d antigen presentation pathway strongly inhibits the ability of infected DCs to activate CD1d-restricted NKT cells. Given that the interaction with CD1d-expressing DCs is central to the ability of NKT cells to regulate immunity, these data suggest that interference with the CD1d antigen presentation pathway represents an HIV-1 strategy to evade innate cellular immune responses and imply a role for the innate-like CD1d-restricted NKT cells in the host defense against HIV-1.

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Human Immunodeficiency Virus Type 1-Hepatitis C Virus Coinfection: Intraindividual Comparison of Cellular Immune Responses against Two Persistent Viruses

Journal of Virology ◽

10.1128/jvi.76.6.2817-2826.2002 ◽

2002 ◽

Vol 76 (6) ◽

pp. 2817-2826 ◽

Cited By ~ 69

Author(s):

Georg M. Lauer ◽

Tam N. Nguyen ◽

Cheryl L. Day ◽

Gregory K. Robbins ◽

Theresa Flynn ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Immune Responses ◽

T Lymphocyte ◽

Viral Loads ◽

Cellular Immune Responses ◽

Immunodeficiency Virus ◽

Cellular Immune ◽

Lymphocyte Responses ◽

Hiv 1

ABSTRACT Both human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) lead to chronic infection in a high percentage of persons, and an expanding epidemic of HIV-1-HCV coinfection has recently been identified. These individuals provide an opportunity for simultaneous assessment of immune responses to two viral infections associated with chronic plasma viremia. In this study we analyzed the breadth and magnitude of the CD8+- and CD4+-T-lymphocyte responses in 22 individuals infected with both HIV-1 and HCV. A CD8+-T-lymphocyte response against HIV-1 was readily detected in all subjects over a broad range of viral loads. In marked contrast, HCV-specific CD8+-T-lymphocyte responses were rarely detected, despite viral loads in plasma that were on average 1,000-fold higher. The few HCV-specific responses that were observed were relatively weak and limited in breadth. CD4-proliferative responses against HIV-1 were detected in about half of the coinfected subjects tested, but no proliferative response against any HCV protein was found in these coinfected persons. These data demonstrate a major discordance in immune responses to two persistent RNA viruses. In addition, they show a consistent and profound impairment in cellular immune responses to HCV compared to HIV-1 in HIV-1-HCV-coinfected persons.

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Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen

Journal of General Virology ◽

10.1099/vir.0.79869-0 ◽

2004 ◽

Vol 85 (8) ◽

pp. 2407-2419 ◽

Cited By ~ 41

Author(s):

B. Mäkitalo ◽

P. Lundholm ◽

J. Hinkula ◽

C. Nilsson ◽

K. Karlén ◽

...

Keyword(s):

Immune Responses ◽

T Lymphocyte ◽

Protective Efficacy ◽

Viral Rna ◽

Post Challenge ◽

Cellular Immune Responses ◽

Immunodeficiency Virus ◽

Cellular Immune ◽

Hiv 1 ◽

Rna Levels

The immunogenicity and protective efficacy of a DNA and recombinant modified vaccinia Ankara (MVA) vaccine administered by two different routes were investigated. DNA expressing HIV-1 IIIB env, gag, RT, rev, tat and nef, and MVA expressing HIV-1 IIIB nef, tat and rev and simian immunodeficiency virus (SIV) macJ5 gag/pol and vaccinia HIV-1 env, were used as immunogens. Four cynomolgus macaques received DNA intramuscularly (i.m.) at month 0 and intrarectally (i.r.) and intra-orally (i.o.) at 2 months, followed by MVA i.m. at 4 months and i.r. and i.o. at 8 months. Another group of four monkeys received the same immunogens but only i.m.. Overall, stronger cellular immune responses measured by ELISPOT and T-cell proliferation assay were detected in the group primed i.m. and boosted mucosally. Following homologous intravenous simian-human immunodeficiency virus (SHIV) challenge, one of eight vaccinated animals was completely protected. This monkey, immunized i.m. and i.r.+i.o., exhibited the highest levels of HIV Env, Nef and Tat antibodies, high HIV Tat cytotoxic T-lymphocyte activity and T-lymphocyte proliferative responses to HIV Env. Four weeks post-challenge none of the monkeys immunized i.m. and i.r.+i.o., and only two out of four animals immunized i.m., demonstrated detectable plasma viral RNA levels. In contrast, all eight control animals had demonstrable plasma viral RNA levels 4 weeks post-challenge. Thus, stronger cellular immune responses and reduction of challenge virus burden were demonstrated in animals immunized i.m. as well as mucosally, compared with animals immunized i.m. only. The breadth and magnitude of the induced immune responses correlated with protective efficacy.

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