The development of vaccines is one of the most significant medical accomplishments which has helped to eradicate a large number of diseases It has undergone an evolutionary process from live attenuated pathogen vaccine to killed whole organisms or inactivated toxins (toxoids), each of them having its own advantages and disadvantages The crucial parameters in vaccination are the generation of memory response and protection against infection, while an important aspect is the effective delivery of antigen in an intelligent manner to evoke a robust immune response In this regard, nanotechnology is greatly contributing to developing efficient vaccine adjuvants and delivery systems These can protect the encapsulated antigen from the host’s in-vivo environment and releasing it in a sustained manner to induce a long-lasting immunostimulatory effect In view of this, the present review article summarizes nanoscale-based adjuvants and delivery vehicles such as viral vectors, virus-like particles and virosomes; non-viral vectors namely nanoemulsions, lipid nanocarriers, biodegradable and non-degradable nanoparticles, calcium phosphate nanoparticles, colloidally stable nanoparticles, proteosomes; and pattern recognition receptors covering c-type lectin receptors and toll-like receptors

https://www.mdpi.com/1999-4923/13/4/455/pdf

An Overview of Nanocarrier-Based Adjuvants for Vaccine Delivery.

In addition to the paternal genome, spermatozoa carry several intrinsic factors, including organelles (e.g., centrioles and mitochondria) and molecules (e.g., proteins and RNAs), which are involved in important steps of reproductive biology such as spermatogenesis, sperm maturation, oocyte fertilization and embryo development. These factors constitute potential biomarkers of "viable sperm" and male fertility status and may become major assets for diagnosing instances of idiopathic male infertility in both humans and livestock animals. A better understanding of the mechanism of action of these sperm intrinsic factors in the regulation of reproductive and developmental processes still presents a major challenge that must be addressed. This review assembles the main data regarding morpho-functional and intrinsic sperm features that are associated with male infertility, with a particular focus on microRNA (miRNA) molecules.

/pdf/from-sperm-motility-to-sperm-borne-microrna-signatures-new-2jw1ktame4.pdf

From Sperm Motility to Sperm-Borne microRNA Signatures: New Approaches to Predict Male Fertility Potential.

Methods to improve the immunogenicity of plasmid DNA vaccines.

BACKGROUND
The ALVAC/gp120 + MF59 vaccines in the HVTN 702 efficacy trial did not prevent HIV-1 acquisition. Vaccine-matched immunological endpoints that were correlates of HIV-1 acquisition risk in RV144 were measured in HVTN 702 and evaluated as correlates of HIV-1 acquisition.


METHODS
Among 1893 HVTN 702 female vaccinees, 60 HIV-1-seropositive cases and 60 matched seronegative non-cases were sampled. HIV-specific CD4+ T-cell and binding antibody responses were measured 2 weeks post-fourth and fifth immunizations. Cox proportional hazards models assessed pre-specified responses as predictors of HIV-1 acquisition.


RESULTS
The HVTN 702 Env-specific CD4+ T-cell response rate was significantly higher than in RV144 (63% vs. 40%, P = 0.03) with significantly lower IgG binding antibody response rate and magnitude to 1086.C V1V2 (67% vs. 100%, P< 0.001; Pmag< 0.001). Although no significant univariate associations were observed between any T-cell or binding antibody response and HIV-1 acquisition, significant interactions were observed (multiplicity-adjusted P<=0.03). Among vaccinees with high IgG A244 V1V2 binding antibody responses, vaccine-matched CD4+ T-cell endpoints associated with decreased HIV-1 acquisition (estimated hazard ratios = 0.40-0.49 per 1-SD increase in CD4+ T-cell endpoint).


CONCLUSIONS
HVTN 702 and RV144 had distinct immunogenicity profiles. However, both identified significant correlations (univariate or interaction) for IgG V1V2 and polyfunctional CD4+ T-cells with HIV-1 acquisition.

Analysis of the HVTN 702 Phase 2b-3 HIV-1 vaccine trial in South Africa assessing RV144 antibody and T-cell correlates of HIV-1 acquisition risk.

IFNL3-adjuvanted HCV DNA vaccine reduces regulatory T cell frequency and increases virus-specific T cell responses.

BACKGROUND The Pox-Protein Public-Private Partnership is performing a suite of trials to evaluate the bivalent subtype C envelope protein (TV1.C and 1086.C glycoprotein 120) vaccine in the context of different adjuvants and priming agents for human immunodeficiency virus (HIV) type 1 (HIV-1) prevention. METHODS In the HIV Vaccine Trials Network 111 trial, we compared the safety and immunogenicity of DNA prime followed by DNA/protein boost with DNA/protein coadministration injected intramuscularly via either needle/syringe or a needle-free injection device (Biojector). One hundred thirty-two healthy, HIV-1-uninfected adults were enrolled from Zambia, South Africa, and Tanzania and were randomized to 1 of 6 arms: DNA prime, protein boost by needle/syringe; DNA and protein coadministration by needle/syringe; placebo by needle/syringe; DNA prime, protein boost with DNA given by Biojector; DNA and protein coadministration with DNA given by Biojector; and placebo by Biojector. RESULTS All vaccinations were safe and well tolerated. DNA and protein coadministration was associated with increased HIV-1 V1/V2 antibody response rate, a known correlate of decreased HIV-1 infection risk. DNA administration by Biojector elicited significantly higher CD4+ T-cell response rates to HIV envelope protein than administration by needle/syringe in the prime/boost regimen (85.7% vs 55.6%; P = .02), but not in the coadministration regimen (43.3% vs 48.3%; P = .61). CONCLUSIONS Both the prime/boost and coadministration regimens are safe and may be promising for advancement into efficacy trials depending on whether cellular or humoral responses are desired. CLINICAL TRIALS REGISTRATION South African National Clinical Trials Registry (application 3947; Department of Health [DoH] no. DOH-27-0715-4917) and ClinicalTrials.gov (NCT02997969).

/pdf/phase-1-human-immunodeficiency-virus-hiv-vaccine-trial-to-hbtddbxmei.pdf

Phase 1 Human Immunodeficiency Virus (HIV) Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Subtype C DNA and MF59-Adjuvanted Subtype C Envelope Protein.

Multiple approaches utilizing viral and DNA vectors have shown promise in the development of an effective vaccine against HIV. In this study, an alternative replication-defective flavivirus vector, RepliVax (RV), was evaluated for the delivery of HIV-1 immunogens. Recombinant RV-HIV viruses were engineered to stably express clade C virus Gag and Env (gp120TM) proteins and propagated in Vero helper cells. RV-based vectors enabled efficient expression and correct maturation of Gag and gp120TM proteins, were apathogenic in a sensitive suckling mouse neurovirulence test, and were similar in immunogenicity to recombinant poxvirus NYVAC-HIV vectors in homologous or heterologous prime-boost combinations in mice. In a pilot NHP study, immunogenicity of RV-HIV viruses used as a prime or boost for DNA or NYVAC candidates was compared to a DNA prime/NYVAC boost benchmark scheme when administered together with adjuvanted gp120 protein. Similar neutralizing antibody titers, binding IgG titers measured against a broad panel of Env and Gag antigens, and ADCC responses were observed in the groups throughout the course of the study, and T cell responses were elicited. The entire data demonstrate that RV vectors have the potential as novel HIV-1 vaccine components for use in combination with other promising candidates to develop new effective vaccination strategies.

/pdf/recombinant-hiv-1-vaccine-candidates-based-on-replication-4p8ux1crkh.pdf

Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector.

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Phase 1 Human Immunodeficiency Virus (HIV) Vaccine Trial to Evaluate the Safety and Immunogenicity of HIV Subtype C DNA and MF59-Adjuvanted Subtype C Envelope Protein.

Recombinant HIV-1 vaccine candidates based on replication-defective flavivirus vector.