Development of TNFSF as molecular adjuvants for ALVAC HIV-1 vaccines

Liu, Jun; Ostrowski, Mario

doi:10.4161/hv.6.4.10867

Cited by 9 publications

(6 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TNFSF molecules are type II transmembrane proteins that have a conserved tumor necrosis factor homology domain at their C-termini [ 15 ]. Many TNFSF members are immune costimulatory molecules, among which CD40 ligand (CD40L), B cell activating factor (BAFF), and a proliferation-inducing ligand (APRIL) are pivotal for B cell costimulation.…”

Section: Tnfsf Molecules-cd40l Baff and Aprilmentioning

confidence: 99%

Development of targeted adjuvants for HIV-1 vaccines

Liu

Ostrowski

2017

AIDS Res Ther

Self Cite

View full text Add to dashboard Cite

Finding new adjuvants is an integrated component of the efforts in developing an effective HIV-1 vaccine. Compared with traditional adjuvants, a modern adjuvant in the context of HIV-1 prevention would elicit a durable and potent memory response from B cells, CD8+ T cells, and NK cells but avoid overstimulation of HIV-1 susceptible CD4+ T cells, especially at genital and rectal mucosa, the main portals for HIV-1 transmission. We briefly review recent advances in the studies of such potential targeted adjuvants, focusing on three classes of molecules that we study: TNFSF molecules, TLRs agonists, and NODs agonists.

show abstract

Section: Tnfsf Molecules-cd40l Baff and Aprilmentioning

confidence: 99%

Development of targeted adjuvants for HIV-1 vaccines

Liu

Ostrowski

2017

AIDS Res Ther

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cognate antigen binding to a B-cell receptor alongside CD40 ligand (CD40L or CD154) engagement with CD40 receptors leads to the generation of a successful adaptive immune response (47). Because of its role in this process, CD40L has been tested as an adjuvant for viral vaccines against influenza, herpes simplex virus (HSV), and HIV, and cancer (19,26,48). CD40L has also been tested as an HIV vaccine adjuvant in a DNA prime recombinant modified vaccine Ankara (MVA) boost strategy in rhesus macaques.…”

Section: Discussionmentioning

confidence: 99%

“…CD40L belongs to the tumor necrosis factor superfamily (TNFSF) (19,20). In its membrane-bound form, CD40L is mainly expressed on activated CD4 ϩ T cells, while its receptor, CD40, is expressed on immature dendritic cells (DCs), B cells, and other immune and nonimmune cells.…”

mentioning

confidence: 99%

Expression of CD40L by the ALVAC-Simian Immunodeficiency Virus Vector Abrogates T Cell Responses in Macaques

Castro

Gordon

et al. 2020

J Virol

Self Cite

View full text Add to dashboard Cite

Immunization with recombinant ALVAC/gp120 alum vaccine provided modest protection from human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) acquisition in humans and macaques. Vaccine-mediated protection was associated with the elicitation of IgG against the envelope V2 loop and of envelope-specific CD4+ T cell responses. We hypothesized that the simultaneous expression of the costimulatory molecule CD40L (CD154) by the ALVAC-HIV vector could increase both protective humoral and cellular responses. We engineered an ALVAC-SIV coexpressing CD40L with SIVmac251 (ALVAC-SIV/CD40L) gag, pol, and env genes. We compared its immunogenicity in macaques with that of a canonical ALVAC-SIV, with both given as a vector-prime/gp120 in alum boost strategy. The ALVAC-SIV/CD40L was superior to the ALVAC-SIV regimen in inducing binding and tier 1 neutralizing antibodies against the gp120. The increase in humoral responses was associated with the expression of the membrane-bound form of the CD40L by CD4+ T cells in lymph nodes. Unexpectedly, the ALVAC-SIV/CD40L vector had a blunting effect on CD4+ Th1 helper responses and instead favored the induction of myeloid-derived suppressor cells, the immune-suppressive interleukin-10 (IL-10) cytokine, and the down-modulatory tryptophan catabolism. Ultimately, this strategy failed to protect macaques from SIV acquisition. Taken together, these results underlie the importance of balanced vaccine-induced activating versus suppressive immune responses in affording protection from HIV. IMPORTANCE CD40-CD40 ligand (CD40L) interaction is crucial for inducing effective cytotoxic and humoral responses against pathogens. Because of its immunomodulatory function, CD40L has been used to enhance immune responses to vaccines, including candidate vaccines for HIV. The only successful vaccine ever tested in humans utilized a strategy combining canarypox virus-based vector (ALVAC) together with an envelope protein (gp120) adjuvanted in alum. This strategy showed limited efficacy in preventing HIV-1/SIV acquisition in humans and macaques. In both species, protection was associated with vaccine-induced antibodies against the HIV envelope and CD4+ T cell responses, including type 1 antiviral responses. In this study, we tested whether augmenting CD40L expression by coexpressing it with the ALVAC vector could increase the protective immune responses. Although coexpression of CD40L did increase humoral responses, it blunted type 1 CD4+ T cell responses against the SIV envelope protein and failed to protect macaques from viral infection.

show abstract

“…For example, costimulatory molecule B7.2 delivered through the vector HIV pCgag/pol enhanced the functioning of cytotoxic T lymphocytes [ 62 ]. Similarly, TNF superfamily ligands (TNFSFL) have been shown to improve the efficacy of ALVAC HIV-1 vaccines in a Phase III clinical trial [ 63 ]. Several other costimulatory molecules are being researched for increasing the efficacy of newer vaccines.…”

Section: Viral Vectors Alternative Delivery Systems and Costimulmentioning

confidence: 99%

HIV Vaccine: Recent Advances, Current Roadblocks, and Future Directions

Rubens

Ramamoorthy

Shehadeh

et al. 2015

Journal of Immunology Research

View full text Add to dashboard Cite

HIV/AIDS is a leading cause of mortality and morbidity worldwide. In spite of successful interventions and treatment protocols, an HIV vaccine would be the ultimate prevention and control strategy. Ever since identification of HIV/AIDS, there have been meticulous efforts for vaccine development. The specific aim of this paper is to review recent vaccine efficacy trials and associated advancements and discuss the current challenges and future directions. Recombinant DNA technologies greatly facilitated development of many viral products which were later incorporated into vectors for effective vaccines. Over the years, a number of scientific approaches have gained popularity and include the induction of neutralizing antibodies in late 1980s, induction of CD8 T cell in early 1990s, and combination approaches currently. Scientists have hypothesized that stimulation of right sequences of somatic hypermutations could induce broadly reactive neutralizing antibodies (bnAbs) capable of effective neutralization and viral elimination. Studies have shown that a number of host and viral factors affect these processes. Similarly, eliciting specific CD8 T cells immune responses through DNA vaccines hold future promises. In summary, future studies should focus on the continuous fight between host immune responses and ever-evasive viral factors for effective vaccines.

show abstract

Development of TNFSF as molecular adjuvants for ALVAC HIV-1 vaccines

Cited by 9 publications

References 36 publications

Development of targeted adjuvants for HIV-1 vaccines

Development of targeted adjuvants for HIV-1 vaccines

Expression of CD40L by the ALVAC-Simian Immunodeficiency Virus Vector Abrogates T Cell Responses in Macaques

HIV Vaccine: Recent Advances, Current Roadblocks, and Future Directions

Contact Info

Product

Resources

About