The immune responses of the prime-boost regimen with rBCG-E12 and rDIs-E12 candidate vaccine

Background: Human papillomavirus (HPV) is the main biological agent causing sexually transmitted diseases (STDs), including precancerous lesions and several types of prevalent cancers. To date, numerous types of vaccines are designed to prevent high-risk HPV. However, their prophylactic effect is not the same and does not clear previous infections. Therefore, there is an urgent need for developing therapeutic vaccines that trigger cell-mediated immune responses for the treatment of HPV. The HPV16 E6 and E7 proteins are ideal targets for vaccine therapy against HPV. Fusion protein vaccines, which include both immunogenic interest protein and an adjuvant for augmenting the immunogenicity effects, are theoretically capable of guarantee the power of the immune system against HPV. Method: A vaccine construct, including HPV16 E6/E7 proteins along with a heat shock protein GP96 (E6/E7-NTGP96 construct), was designed using in silico methods. By the aid of the SWISS-MODEL server, the optimal 3D model of the designed vaccine was selected, followed by physicochemical and molecular parameters were performed using bioinformatics tools. Docking studies were done to evaluate the binding interaction of the vaccine. Allergenicity, immunogenicity, B, and T cell epitopes of the designed construct were predicted. Results: Immunological and structural computational results illustrated that our designed construct is potentially proper for stimulation of cellular and humoral immune responses against HPV. Conclusion: Computational studies showed that the E6/E7-NTGP96 construct is a promising candidate vaccine that needs further in vitro and in vivo evaluations.

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Rapid Appearance of Secondary Immune Responses and Protection from Acute CD4 Depletion after a Highly Pathogenic Immunodeficiency Virus Challenge in Macaques Vaccinated with a DNA Prime/Sendai Virus Vector Boost Regimen

Journal of Virology ◽

10.1128/jvi.75.23.11891-11896.2001 ◽

2001 ◽

Vol 75 (23) ◽

pp. 11891-11896 ◽

Cited By ~ 69

Author(s):

Tetsuro Matano ◽

Munehide Kano ◽

Hiromi Nakamura ◽

Akiko Takeda ◽

Yoshiyuki Nagai

Keyword(s):

T Cells ◽

T Cell ◽

Immune Responses ◽

Sendai Virus ◽

Cell Depletion ◽

Highly Pathogenic ◽

T Cell Depletion ◽

Boost Regimen ◽

Viral Loads ◽

Immunodeficiency Virus

ABSTRACT Heterologous prime/boost regimens are AIDS vaccine candidates because of their potential for inducing cellular immune responses. Here, we have developed a prime/boost regimen leading to rapid control of highly pathogenic immunodeficiency virus infection in macaques. The strategy, priming by an env and nefdeletion-containing simian-human immunodeficiency virus (SHIV) proviral DNA followed by a single booster with a Gag-expressing Sendai virus (SeV-Gag), efficiently induced virus-specific T cells, which were maintained for more than 3 months until challenge. While all naive control macaques showed acute CD4+ T-cell depletion at week 2 after an intravenous SHIV89.6PD challenge, all the macaques vaccinated with the prime/boost regimen were protected from depletion and showed greatly reduced peak viral loads compared with controls. Vaccination with the DNA alone or SeV-Gag alone was not enough to confer the consistent protection from the depletion, although it led to efficient secondary CD8+ T-cell responses at week 2 after challenge. At week 1, a difference in the secondary responses between the protected and the unprotected macaques was clear; rapid augmentation of virus-specific CD8+ T cells was detected in the former but not in the latter. Thus, our results indicate the importance of rapid secondary responses for reduction in the peak viral loads and protection from acute CD4+ T-cell depletion.

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Formulation of chitosan with the polyepitope HIV-1 protein candidate vaccine efficiently boosts cellular immune responses in mice

Pathogens and Disease ◽

10.1093/femspd/ftx098 ◽

2017 ◽

Vol 75 (8) ◽

Cited By ~ 3

Author(s):

Ehsan Ollah Jazaeri ◽

Atiyeh Mahdavi ◽

Asghar Abdoli

Keyword(s):

Immune Responses ◽

Candidate Vaccine ◽

Cellular Immune Responses ◽

Cellular Immune ◽

Hiv 1

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A self-amplifying mRNA COVID-19 vaccine drives potent and broad immune responses at low doses that protects non-human primates against SARS-CoV-2

10.1101/2021.11.08.467773 ◽

2021 ◽

Author(s):

Amy R Rappaport ◽

Sue-Jean Hong ◽

Ciaran D Scallan ◽

Leonid Gitlin ◽

Arvin Akoopie ◽

...

Keyword(s):

Immune Responses ◽

Protective Efficacy ◽

Rhesus Macaques ◽

Geometric Mean ◽

Low Doses ◽

Vaccination Regimen ◽

Preclinical Development ◽

Boost Regimen ◽

Boost Vaccination ◽

Dose Levels

The coronavirus disease 2019 (COVID-19) pandemic continues to spread globally, highlighting the urgent need for safe and effective vaccines that could be rapidly mobilized to immunize large populations. We report the preclinical development of a self-amplifying mRNA (SAM) vaccine encoding a prefusion stabilized severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein and demonstrate potent cellular and humoral immune responses at low doses in mice and rhesus macaques. The homologous prime-boost vaccination regimen of SAM at 3, 10 and 30 μg induced potent neutralizing antibody titers in rhesus macaques following two SAM vaccinations at all dose levels, with the 10 μg dose generating geometric mean titers (GMT) 48-fold greater than the GMT of a panel of SARS-CoV-2 convalescent human sera. Spike-specific T cell responses were observed at all dose levels. SAM vaccination provided protective efficacy against SARS-CoV-2 challenge as both a homologous prime-boost and as a single boost following ChAd prime, demonstrating reduction of viral replication in both the upper and lower airways. Protection was most effective with a SAM prime-boost vaccination regimen at 10 and 30 μg and with a ChAd/SAM heterologous prime-boost regimen. The SAM vaccine is currently being evaluated in clinical trials as both a homologous prime-boost regimen at low doses and as a boost following heterologous prime.

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Immune Responses to Candidate Vaccine Antigens Delivered Through Naked Plasmid and Mycobacterial Vectors

The Open Conference Proceedings Journal ◽

10.2174/2210289201607010153 ◽

2016 ◽

Vol 7 (1) ◽

pp. 153-159

Author(s):

Abu Salim Mustafa

Keyword(s):

Immune Responses ◽

Candidate Vaccine ◽

Vaccine Antigens ◽

Naked Plasmid

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Liver-Directed AAV8 Booster Vaccine Expressing Plasmodium falciparum Antigen Following Adenovirus Vaccine Priming Elicits Sterile Protection in a Murine Model

Frontiers in Immunology ◽

10.3389/fimmu.2021.612910 ◽

2021 ◽

Vol 12 ◽

Author(s):

Mohammad Shahnaij ◽

Mitsuhiro Iyori ◽

Hiroaki Mizukami ◽

Mayu Kajino ◽

Iroha Yamagoshi ◽

...

Keyword(s):

T Cells ◽

Immune Responses ◽

Malaria Vaccine ◽

Infected Mosquito ◽

Great Promise ◽

Adeno Associated Virus ◽

Boost Regimen ◽

Cellular Immune Responses ◽

Virus Serotype ◽

Cellular Immune

Hepatocyte infection by malaria sporozoites is a bottleneck in the life-cycle of Plasmodium spp. including P. falciparum, which causes the most lethal form of malaria. Therefore, developing an effective vaccine capable of inducing the strong humoral and cellular immune responses necessary to block the pre-erythrocytic stage has potential to overcome the spatiotemporal hindrances pertaining to parasite biology and hepatic microanatomy. We recently showed that when combined with a human adenovirus type 5 (AdHu5)-priming vaccine, adeno-associated virus serotype 1 (AAV1) is a potent booster malaria vaccine vector capable of inducing strong and long-lasting protective immune responses in a rodent malaria model. Here, we evaluated the protective efficacy of a hepatotropic virus, adeno-associated virus serotype 8 (AAV8), as a booster vector because it can deliver a transgene potently and rapidly to the liver, the organ malaria sporozoites initially infect and multiply in following sporozoite injection by the bite of an infected mosquito. We first generated an AAV8-vectored vaccine expressing P. falciparum circumsporozoite protein (PfCSP). Intravenous (i.v.) administration of AAV8-PfCSP to mice initially primed with AdHu5-PfCSP resulted in a hepatocyte transduction rate ~2.5 times above that seen with intramuscular (i.m.) administration. This immunization regimen provided a better protection rate (100% sterile protection) than that of the i.m. AdHu5-prime/i.m. AAV8-boost regimen (60%, p < 0.05), i.m. AdHu5-prime/i.v. AAV1-boost (78%), or i.m. AdHu5-prime/i.m. AAV1-boost (80%) against challenge with transgenic PfCSP-expressing P. berghei sporozoites. Compared with the i.m. AdHu5-prime/i.v. AAV1-boost regimen, three other regimens induced higher levels of PfCSP-specific humoral immune responses. Importantly, a single i.v. dose of AAV8-PfCSP recruited CD8+ T cells, especially resident memory CD8+ T cells, in the liver. These data suggest that boost with i.v. AAV8-PfCSP can improve humoral and cellular immune responses in BALB/c mice. Therefore, this regimen holds great promise as a next-generation platform for the development of an effective malaria vaccine.

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