A5057849882- HIV Research and Treatment
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- Immune responses and vaccinations
- Virus-based gene therapy research
- Animal Disease Management and Epidemiology
- Poxvirus research and outbreaks
- T-cell and B-cell Immunology
- Cervical Cancer and HPV Research
- T-cell and Retrovirus Studies
- Vector-Borne Animal Diseases
- Bacillus and Francisella bacterial research
- Phagocytosis and Immune Regulation
- Virology and Viral Diseases
- Herpesvirus Infections and Treatments
- Hepatitis B Virus Studies
- HIV/AIDS Research and Interventions
- Blood groups and transfusion
- Animal Virus Infections Studies
- Reproductive System and Pregnancy
- Immune cells in cancer
- Immunodeficiency and Autoimmune Disorders
- Cytokine Signaling Pathways and Interactions
- Microbial Community Ecology and Physiology
- Antibiotic Resistance in Bacteria
Center for Cancer Research
2018-2025
National Institutes of Health
2019-2025
National Cancer Institute
2016-2025
University of Milan
2011-2018
The development of an effective vaccine to protect against HIV acquisition will be greatly bolstered by in-depth understanding the innate and adaptive responses vaccination. We report here that efficacy DNA/ALVAC/gp120/alum vaccines, based on V2-specific antibodies mediating apoptosis infected cells (V2-ADCC), is complemented efferocytosis, a cyclic AMP (cAMP)-dependent antiphlogistic engulfment apoptotic CD14
ABSTRACT An estimated 10–20 million people worldwide are infected with the deltaretrovirus human T-cell leukemia virus type 1 (HTLV-1). Although most individuals remain asymptomatic, some progress to develop fatal and debilitating disease adult leukemia/lymphoma (ATLL) or HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) a plethora of other inflammatory disorders. In addition, HTLV-1 infection is associated immunosuppression shorter lifespan. protective role for neutralizing...
The efficacy of ALVAC-based HIV and SIV vaccines in humans macaques correlates with antibodies to envelope variable region 2 (V2). We show here that vaccine-induced 1 (V1) inhibit anti-V2 antibody-mediated cytotoxicity reverse their ability block V2 peptide interaction the α4β7 integrin. engineered delete V1 favor an α helix, rather than a β sheet conformation, induced V2-specific ADCC correlating decreased risk acquisition. Removal from HIV-1 clade A/E A244 resulted binding recognizing...
We investigated the impact of monocytes, NK cells, and CD8 + T-cells in primary HTLV-1 infection by depleting cell subsets exposing macaques to either wild type (HTLV-1 WT ) or p12KO mutant unable infect replete animals due a single point mutation orf-I that inhibits its expression. The orf- I encoded p8/p12 proteins counteract cytotoxic favor viral DNA persistence monocytes. Double depletion alone accelerated seroconversion all exposed . In contrast, infectivity was fully restored only when...
The traditional smallpox vaccine, administered by scarification, was discontinued in the general population from 1980, because of absence new cases. However, development an effective prophylactic vaccine against is still necessary, to protect threat deliberate release variola virus for bioterrorism and zoonotic infections, improve safety vaccine. Preventive vaccination remains most control vectors have been developed generate recombinant vaccines that induce same immunogenicity as one. As...
Considering the high number of new cases cervical cancer each year that are caused by human papilloma viruses (HPVs), development an effective vaccine for prevention and therapy HPV-associated cancers, in particular against high-risk HPV-16 genotype, remains a priority. Vaccines expressing E6 E7 proteins detectable all HPV-positive pre-cancerous cells might support treatment HPV-related lesions clear already established tumors. In this study, DNA fowlpox virus recombinants E6F47R mutant...
The ALVAC-HIV clade B/AE and equivalent SIV-based/gp120 + Alum vaccines successfully decreased the risk of virus acquisition in humans macaques. Here, we tested efficacy HIV B/C ALVAC/gp120 vaccine candidates MF59 or different doses Aluminum hydroxide (Alum) against SHIV-Cs varying neutralization sensitivity Low induced higher mucosal V2-specific IgA that increased Tier 2 SHIV-C acquisition. High dosage, contrast, elicited serum IgG to V2 correlated with a 1 negligible antibodies an...
SIV and HIV-based envelope V1-deleted (ΔV1) vaccines, delivered systemically by the DNA/ALVAC/gp120 platform, decrease risk of mucosal or SHIV acquisition more effectively than V1-replete vaccines. Here we investigated induction systemic memory-like NK cells as well antigen-reactive ILC response DNA/ALVAC/gp120-based vaccination their role against SIV/SHIV infection. ΔV1 HIV elicited a higher level TNF-α
The DNA-SIV + ALVAC-SIV gp120 alum boost vaccine regimen induces innate monocyte memory immunity via inflammasome activation, high levels of IL-1 production, emergency myelopoiesis, and the egress CXCR4+CD14+ pre-monocytes from bone marrow. Vaccine-associated is itself associated with decreased risk SIVmac251 acquisition T-cell activation. Interestingly, this also induced CD16+ monocytes that are instead an increased SIV acquisition. Because promotes propagation monocyte-derived suppressor...
The recombinant Canarypox ALVAC-HIV/gp120/alum vaccine regimen was the first to significantly decrease risk of HIV acquisition in humans, with equal effectiveness both males and females. Similarly, an equivalent SIV-based ALVAC decreased virus Indian rhesus macaques sexes following intrarectal exposure low doses SIVmac251. Here, we demonstrate that ALVAC-SIV/gp120/alum is also efficacious female Chinese intravaginal SIVmac251 confirm CD14+ classical monocytes are a strong correlate...
Abstract The human immunodeficiency virus epidemic continues in sub-Saharan Africa, and particularly affects adolescent girls women who have limited access to antiretroviral therapy. Here we report that the risk of vaginal simian (SIV) mac251 acquisition is reduced by more than 90% using a combination vaccine comprising V1-deleted (V2 enhanced) SIV envelope immunogens with topical treatment zinc-finger inhibitor SAMT-247. Following 14 weekly intravaginal exposures highly pathogenic , 80%...
Expression of HPV E5, E6 and E7 oncogenes are likely to overcome the regulation cell proliferation escape immunological control, allowing uncontrolled growth providing potential for malignant transformation. Thus, their three oncogenic products may represent ideal target antigens immunotherapeutic strategies. In previous attempts, we demonstrated that genetic vaccines against recombinant HPV16 antigen were able affect tumor in a pre-clinical mouse model. To improve this anti-HPV strategy...
Human papilloma virus (HPV)-16 is the most prevalent high-risk mucosal genotype. Virus-like-particle (VLP)-based immunogens developed recently have proven to be successful as prophylactic HPV vaccines, but are still too expensive for developing countries. Although vaccinia viruses expressing HPV-16 L1 protein (HPV-L1) been studied, fowlpox-based recombinants represent efficient and safer vectors immunocompromised hosts due their ability elicit a complete immune response natural host-range...
An effective AIDS vaccine should elicit strong humoral and cellular immune responses while maintaining low levels of CD4
Studies suggest that the protection against SIV/simian-human immunodeficiency virus (SHIV) acquisition afforded by SIV/HIV V1 deletion-containing envelope immunogens, delivered DNA/ALVAC vaccine platform, requires multiple innate and adaptive host responses. Anti-inflammatory macrophages tolerogenic dendritic cells (DC-10), together with CD14 + efferocytes, are consistently found to correlate a vaccine-induced decrease in risk of SIV/SHIV acquisition.
The transient depletion of monocytes alone prior to exposure macaques HTLV-1 enhances both HTLV-1WT (wild type) and HTLV-1p12KO (Orf-1 knockout) infectivity, but seroconversion either virus is not sustained over time, suggesting a progressive decrease in expression. These results raise the hypotheses that persistence depends on monocyte reservoir or provides immune evasion benefit. To test these hypotheses, we simultaneously depleted NK cells, CD8+ T (triple depletion) HTLV-1p12KO....
An efficacious human immunodeficiency virus (HIV) vaccine will likely require induction of both mucosal and systemic immune responses. We compared the immunogenicity protective efficacy two mucosal/systemic regimens investigated their effects on rectal microbiome. Rhesus macaques were primed twice mucosally with replication-competent adenovirus type 5 host range mutant (Ad5hr)-simian (SIV) recombinants boosted intramuscularly ALVAC-SIV recombinant plus SIV gp120 protein or DNA for genes...