Advertisement

Topics

Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection.

07:00 EST 23rd February 2018 | BioPortfolio

Summary of "Distinct susceptibility of HIV vaccine vector-induced CD4 T cells to HIV infection."

The concerns raised from adenovirus 5 (Ad5)-based HIV vaccine clinical trials, where excess HIV infections were observed in some vaccine recipients, have highlighted the importance of understanding host responses to vaccine vectors and the HIV susceptibility of vector-specific CD4 T cells in HIV vaccination. Our recent study reported that human Ad5-specific CD4 T cells induced by Ad5 vaccination (RV156A trial) are susceptible to HIV. Here we further investigated the HIV susceptibility of vector-specific CD4 T cells induced by ALVAC, a canarypox viral vector tested in the Thai trial RV144, as compared to Ad5 vector-specific CD4 T cells in the HVTN204 trial. We showed that while Ad5 vector-specific CD4 T cells were readily susceptible to HIV, ALVAC-specific CD4 T cells in RV144 PBMC were substantially less susceptible to both R5 and X4 HIV in vitro. The lower HIV susceptibility of ALVAC-specific CD4 T cells was associated with the reduced surface expression of HIV entry co-receptors CCR5 and CXCR4 on these cells. Phenotypic analyses identified that ALVAC-specific CD4 T cells displayed a strong Th1 phenotype, producing higher levels of IFN-γ and CCL4 (MIP-1β) but little IL-17. Of interest, ALVAC and Ad5 vectors induced distinct profiles of vector-specific CD8 vs. CD4 T-cell proliferative responses in PBMC, with ALVAC preferentially inducing CD8 T-cell proliferation, while Ad5 vector induced CD4 T-cell proliferation. Depletion of ALVAC-, but not Ad5-, induced CD8 T cells in PBMC led to a modest increase in HIV infection of vector-specific CD4 T cells, suggesting a role of ALVAC-specific CD8 T cells in protecting ALVAC-specific CD4 T cells from HIV. Taken together, our data provide strong evidence for distinct HIV susceptibility of CD4 T cells induced by different vaccine vectors and highlight the importance of better evaluating anti-vector responses in HIV vaccination.

Affiliation

Journal Details

This article was published in the following journal.

Name: PLoS pathogens
ISSN: 1553-7374
Pages: e1006888

Links

DeepDyve research library

PubMed Articles [30885 Associated PubMed Articles listed on BioPortfolio]

Mechanisms of fibronectin-binding protein A (FnBPA) vaccine efficacy in Staphylococcus aureus sepsis versus skin infection.

Increasing rates of life-threatening infections and decreasing susceptibility to antibiotics urge an effective vaccine targeting Staphylococcus aureus. Here we investigate the role of cellular immunit...

Analysis of adenovirus-induced immunity to infection with Listeria monocytogenes: Fading protection coincides with declining CD8 T cell numbers and phenotypic changes.

Defining correlates of T cell mediated protection is important in order to accelerate the development of efficient T cell based vaccines conferring long-term immunity. Extensive studies have provided ...

Exploration of the bacterial invasion capacity of Listeria monocytogenes in ZF4 cells.

Despite the results from zebrafish challenged model have demonstrated that Listeria monocytogenes (Lm) has strong adjuvant effects when this attenuated pathogenic bacteria is viewed as aquaculture vac...

Live attenuated influenza vaccine viral vector induces functional cytotoxic T-cell immune response against foreign CD8+ T-cell epitopes inserted into NA and NS1 genes using the 2A self-cleavage site.

The development of viral vector vaccines against various pathogens for which conventional vaccination approaches are not applicable has been a priority for a number of years. One promising approach is...

Taking a bite out of nutrition and arbovirus infection.

Nutrition is a key factor in host-pathogen defense. Malnutrition can increase both host susceptibility and severity of infection through a number of pathways, and infection itself can promote nutritio...

Clinical Trials [15573 Associated Clinical Trials listed on BioPortfolio]

Safety of and Immune Response to an HIV DNA Plasmid Vaccine Followed by HIV Adenoviral Vector Vaccine in Healthy African Adults

The purpose of this study is to evaluate the safety and tolerability of and immune response to an HIV DNA vaccine followed by an adenoviral vector HIV vaccine in healthy African adults at ...

Safety and Efficacy of T Cell Genetic Immunotherapy for HIV

This study uses autologous (one's own) CD4 T cells modified with a viral vector expressing a genetic antisense targeting HIV, this vector is called VRX496. Study treatment is by intraveno...

Safety and Effectiveness of an HIV DNA Vaccine Followed by an HIV Adenoviral Vector Vaccine for Prevention of HIV Infection in the Americas and Africa

The development of a safe and effective vaccine is the best strategy for preventing the spread of HIV-1. The purpose of this study is to determine the safety and effectiveness of and immu...

Extended Follow-Up of Participants in Preventive HIV Vaccine Studies in Uganda

Two previous studies of an HIV preventive vaccine, the STEP study and the Phambili study, were halted because people who received the vaccine were more likely to become infected with HIV. ...

Vaccine Therapy and Cytokine-Induced Killer Cells in Treating Patients With Recurrent Glioblastoma

This pilot early phase I trial studies the side effects of vaccine therapy and cytokine-induced killer cells in treating patients with glioblastoma that has come back. Vaccines made from a...

Medical and Biotech [MESH] Definitions

A combined vaccine used to prevent infection with diphtheria and tetanus toxoid. This is used in place of DTP vaccine (DIPHTHERIA-TETANUS-PERTUSSIS VACCINE) when PERTUSSIS VACCINE is contraindicated.

Vaccines or candidate vaccines containing antigenic polysaccharides from Haemophilus influenzae and designed to prevent infection. The vaccine can contain the polysaccharides alone or more frequently polysaccharides conjugated to carrier molecules. It is also seen as a combined vaccine with diphtheria-tetanus-pertussis vaccine.

Techniques for separating distinct populations of cells.

A live vaccine containing attenuated poliovirus, types I, II, and III, grown in monkey kidney cell tissue culture, used for routine immunization of children against polio. This vaccine induces long-lasting intestinal and humoral immunity. Killed vaccine induces only humoral immunity. Oral poliovirus vaccine should not be administered to immunocompromised individuals or their household contacts. (Dorland, 28th ed)

A bacterial vaccine for the prevention of brucellosis in man and animal. Brucella abortus vaccine is used for the immunization of cattle, sheep, and goats.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Human Immuno Deficiency Virus (HIV)
Human Immunodeficiency Virus (HIV), the causative agent of AIDS. The Human Immunodeficiency Virus, more commonly known as HIV, is a member of the lentivirus sub-set of the retrovirus family of pathogens. It causes AIDS, or Acquired Immuno Deficiency Sy...

Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe, its toxins or one ...


Searches Linking to this Article