Recombinant Subunit Vaccine Research Articles

Intranasal (IN) COVID-19 vaccines - a breakthrough.

Emerging variants of COVID-19 have threatened the effectiveness of intramuscular (IM) vaccines since that are made to target only the spike protein. Development of Intranasal (IN) vaccination has been proven to provide both the mucosal and systemic immune responses for broader and long lasting protection. Many IN vaccine candidates (virus-vectored vaccines, recombinant subunit vaccines and live attenuated vaccines) are in different phases of clinical trials and in near future many companies would be releasing their vaccines into the drug market. Potential advantages of IN vaccination over IM vaccination makes them ideal to be administered in children and developing populations of the world. This paper focuses on the very recent developments in intranasal vaccination with a spotlight on their safety and efficacy concerns. IN vaccination can prove to be game-changer in handling COVID-19 and potential viral contagious diseases in future.

Inulin acetate as a novel recombinant subunit vaccine carrier for immunization of tilapia against tilapia lake virus

Tilapia lake virus (TiLV) is highly contagious and pathogenic to tilapia, causing enormous economic losses in tilapia industry. Up to now, there is no commercial vaccine is available for against TiLV infection. Therefore, a novel vaccine with high immune efficacy is urgently-needed. In this study, we examined the efficacy of subunit vaccine against TiLV through intramuscular injection using inulin acetate (InAc) nanoparticles encapsulation. The S2 protein (encoded by segment 2 gene of TiLV) was used as the antigen and the delivery system was named as InAc-S2. The toxicity analysis showed InAc-S2 had no significant influence on fishes growing and development. Meanwhile, we found InAc-S2 has a dual-release pattern (initial burst release and sustained release) in antigen release. Subsequently, tilapia was injected intramuscularly by different treatments (PBS, InAc, S2, and InAc-S2), and the immune protective effect induced by these treatments was analyzed. We found a powerful and long-lasting humoral or cellular immune response (serum antibody production, immune-related parameters and immune-related genes expression) can be induced in fishes by injected with InAc-S2 in comparison with those injected with S2 antigen alone. Moreover, a relative higher survival rate was observed in fish vaccinated with InAc-S2 at the dose of 4 μg protein/g of fish (with the relative percentage survival of 58.6%). Overall, this study for the first time demonstrated the potential of InAc as subunit vaccine carrier against TiLV infection and provide a reference to novel vaccine development in aquaculture.

Recombinant Toxoplasma gondii Calreticulin protein provides partial protection against acute and chronic toxoplasmosis

Toxoplasma gondii, a highly prevalent apicomplexan pathogen, can cause serious or even fatal toxoplasmosis in both animals and humans. Immunoprophylaxis is considered a promising strategy for controlling this disease. Calreticulin (CRT) is known as a pleiotropic protein, which is critical for calcium storage and phagocytosis of apoptotic cells. Our study examined the protective effects of recombinant T. gondii Calreticulin (rTgCRT) as a recombinant subunit vaccine against the T. gondii challenge in mice. Here, rTgCRT was successfully expressed in vitro using prokaryptic expression system. Polyclonal antibody (pAb) has been prepared by immunizing Sprague Dawley rats with rTgCRT. Western blotting showed that rTgCRT and natural TgCRT protein were recognized by serum of T. gondii infected mice and rTgCRT pAb, respectively. T lymphocyte subsets and antibody response were monitored using flow cytometry and enzyme-linked immunosorbent assay (ELISA). The results showed that ISA 201 rTgCRT could stimulate lymphocyte proliferation and induce high levels of total and subclasses of IgG. After the RH strain challenge, a longer survival period was given by the ISA 201 rTgCRT vaccine compared to the control groups; after infection with the PRU strain, we observed a 100% survival rate and a significant reduction in cysts load and size. In the neutralization test, high concentrations of rat-rTgCRT pAb provided 100% protection, while in the passive immunization trial, only weak protection was observed after RH challenge, indicating that rTgCRT pAb needs further modification to improve its activity in vivo. Taken together, these data confirmed that rTgCRT can trigger strong cellular and humoral immune responses against acute and chronic toxoplasmosis.

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for the Medigen COVID-19 protein vaccine

The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group has prepared standardized templates to describe the key considerations for the benefit-risk assessment of several vaccine platform technologies, including protein subunit vaccines. This article uses the BRAVATO template to review the features of the MVC-COV1901 vaccine, a recombinant protein subunit vaccine based on the stabilized pre-fusion SARS-CoV-2 spike protein S-2P, adjuvanted with CpG 1018 and aluminum hydroxide, manufactured by Medigen Vaccine Biologics Corporation in Taiwan. MVC-COV1901 vaccine is indicated for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 12 years of age and older. The template offers details on basic vaccine information, target pathogen and population, characteristics of antigen and adjuvant, preclinical data, human safety and efficacy data, and overall benefit-risk assessment.The clinical development program began in September 2020 and based on demonstration of favorable safety and immunogenicity profiles in 11 clinical trials in over 5,000 participants, it has been approved for emergency use based on immunobridging results for adults in Taiwan, Estwatini, Somaliland, and Paraguay. The main clinical trials include placebo-controlled phase 2 studies in healthy adults (CT-COV-21), adolescents (CT-COV-22), and elderly population (CT-COV-23) as well as 3 immunobridging phase 3 trials (CT-COV-31, CT-COV-32, and CT-COV-34) in which MVC-COV1901 was compared to AZD1222. There are also clinical trials studying MVC-COV1901 as homologous and heterologous boosters (CT-COV-24 and CT-COV-25).The totality of evidence based on ∼3 million vaccinees to date includes a mostly clean safety profile, with adverse events mostly being mild and self-limiting in both clinical development and post-marketing experience, proven immunogenic response, and real-world effectiveness data. The immunogenic profile demonstrates that MVC-COV1901 induces high levels of neutralizing and binding antibodies against SARS-CoV-2. There is a dose-dependent response and a significant correlation between binding and neutralizing antibody activity. Antigen-specific T-cell responses, particularly a Th1-biased immune response characterized by high levels of interferon gamma and IL-2 cytokines, have also been observed. Coupled with this, MVC-COV1901 has favorable thermostability and better safety profiles when compared to other authorized vaccines from different platforms, which make it potentially a good candidate for vaccine supply chains in global markets.

Combinations but Not a Single PlpE Epitope Induces Host Protective Immunity against Pasteurella multocida.

Pasteurella multocida is the causative agent of a wide range of diseases (pasteurellosis) and a zoonotic pathogen in humans. Recombinant subunit vaccines are hot spots in recent pasteurellosis vaccine development. A chimeric vaccine is also constructed for rabbit hemorrhagic disease virus (RHDV) protective antigen VP60 chimeric with fragments of Pasteurella multocida protective antigen PlpE. The protective efficacy of the chimeric vaccine against P. multocida is not as high as that of PlpE, and the reason is not well known. In this study, we analyzed the linear B-cell epitopes of PlpE and then assessed the protective efficacy of these epitopes and their combinations. It was found that the immunodominant region of PlpE was mainly located in the region between the 21st to the 185th amino acids from the N terminus. Overlapping peptide scanning results demonstrated that this region contained six nonoverlapping epitopes, and epitope E was the predominant epitope. Chimeric protein antigens were constructed of single nonoverlapping PlpE epitopes or their combinations chimeric with the RHDV VP60 P domain. Immunization with recombinant antigen chimeric with a single PlpE epitope exhibited poor immunoprotection, whereas immunization with recombinant antigen chimeric with PlpE epitope combinations (epitopes A and E; epitopes C and E; epitopes A, C, and E; and epitopes B, D, and F) exhibited significant immunoprotection. In a word, P. multocida protective antigen PlpE contained six nonoverlapping linear B-cell epitopes, and combinations but not a single epitope induced host protective immunity. Our work will give help for future chimeric vaccine design.

Human adenovirus type 7 virus-like particle vaccine induces Dendritic cell maturation through the TLR4/NF-κB pathway and is highly immunogenic

Human adenovirus type 7 (HAdv-7) infection is the main cause of upper respiratory tract infection, bronchitis and pneumonia in children. At present, there are no anti-adenovirus drugs or preventive vaccines in the market. Therefore, it is necessary to develop a safe and effective anti-adenovirus type 7 vaccine. In this study, we designed a virus-like particle vaccine expressing the epitopes of hexon and penton of adenovirus type 7 with hepatitis B core protein (HBc) as the vector to induce high-level humoral and cellular immune responses. To evaluate the effectiveness of the vaccine, we first detected the expression of molecular markers on the surface of antigen presenting cells and the secretion of proinflammatory cytokines in vitro. We then measured the levels of neutralizing antibodies and T cell activation in vivo. The results showed that the HAdv-7 virus-like particles (VLPs) recombinant subunit vaccine could activate the innate immune response, including the TLR4/NF-κB pathway which upregulated the expression of MHC II, CD80, CD86, CD40 and cytokines. The vaccine also triggered a strong neutralizing antibody and cellular immune response and activated T lymphocytes. Therefore, the HAdv-7 VLPs promoted humoral and cellular immune responses, thereby potentially enhancing protection against HAdv-7 infection.

Safety and immunogenicity of a protein subunit COVID-19 vaccine (ZF2001) in healthy children and adolescents aged 3–17 years in China: a randomised, double-blind, placebo-controlled, phase 1 trial and an open-label, non-randomised, non-inferiority, phase 2 trial

Safety and immunogenicity of a protein subunit COVID-19 vaccine (ZF2001) in healthy children and adolescents aged 3–17 years in China: a randomised, double-blind, placebo-controlled, phase 1 trial and an open-label, non-randomised, non-inferiority, phase 2 trial

Uptake of COVID-19 Vaccination and Its Associated Factors among College Students in China: A Nationwide Cross-Sectional Study.

Our study aims to assess the uptake of COVID-19 vaccination and its associated factors among Chinese college students. A web-based cross-sectional study was conducted from 18 May to 17 June 2022. A total of 3916 participants were included. The coverage of the first dose, complete vaccination and booster vaccination among college students was 99.49%, 81.96% and 79.25%, respectively. College students with an older age (AOR: 0.72, 95% CI: 0.57-0.90), non-medical major (0.47, 0.37-0.61) and studying in north-east China (0.35, 0.22-0.58) were less likely to complete vaccination. Individuals who were female (1.62, 1.35-1.94) and received a recombinant subunit vaccine (8.05, 5.21-12.45) were more likely to complete vaccination. Non-medical students (0.56, 0.43-0.73) and students studying in north-east China (0.28, 0.16-0.49) were less likely to receive a booster dose, while female students (1.51, 1.23-1.85) had a higher likelihood. The main reason for being unvaccinated was "contraindication" (75.00%), and the main reason for not receiving a booster dose was "being too busy to attend to it" (61.37%). This study demonstrated a high adherence to the COVID-19 vaccination policy among Chinese college students. Targeted strategies should be applied to remove barriers to COVID-19 vaccination among college students.

The Efficacy and Safety of SARS-CoV-2 Vaccinations in People with Multiple Sclerosis

While people with multiple sclerosis (MS) are not more likely to contract COVID-19, the incidences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related complications may be higher for people with MS who have comorbidities or who are taking certain disease modifying therapies (DMT). Robert Shin, Professor of Neurology at MedStar Georgetown University Hospital, Washington, D.C., USA, and Deborah Fuller, Department of Microbiology, University of Washington School of Medicine, and Associate Director of the Washington National Primate Research Center, Seattle, Washington, USA, first discussed why vaccinations against SARS-CoV-2 should be recommended to people with MS. They then discussed evidence that suggests that the antibody response following vaccination may be dampened in people taking some DMTs, especially those that deplete CD20+ B cells; however, T cell responses to vaccinations may also provide protection. There is also evidence that messenger RNA (mRNA) SARS-CoV-2 vaccines, as opposed to viral vector or recombinant protein subunit vaccines, and boosters may lead to a better antibody response. Vaccine responses vary between patients taking different sphinogosine-1-phosphate (S1P) receptor modulators, being low for fingolimod and high for next generation S1P receptor modulators. Overall, more studies of vaccine response and timing are needed to best update the guidelines for people with MS.

Analysis of neutralizing antibodies to COVID-19 inactivated or subunit recombinant vaccines in hospitalized patients with liver dysfunction.

The neutralizing antibodies (NAbs) response after COVID-19 vaccination after liver dysfunction is unclear. In this study, we evaluated the NAbs response after COVID-19 vaccination in hospitalized patients suffering from liver dysfunction. In this cross-sectional study with longitudinal follow-up, we enrolled eligible patients with liver dysfunction and healthy volunteers with full-course COVID-19 vaccination. Blood samples were collected for the NAbs testing at the time of admission and after treatment. Multiple regression analysis to assess independent risk factors affecting NAbs response. A total of 137 patients and 134 healthy controls (HC) were enrolled. Both seropositivity (65.7% vs 80.6%, p<0.01) and titer (3.95 vs 4.94 log2 AU/ml, p<0.001) of NAbs in patients were significantly lower than that in HC. The decrease of antibody titer in patients was significantly faster than that in HC. After adjusting for potential confounding factors, males (odds ratio [OR]: 0.17; 95% confidence interval [CI]: 0.06, 0.46; p<0.001) and severe liver damage (OR: 0.30; 95% CI: 0.12, 0.71; p<0.01) were significantly associated with reduction of the probability of NAbs seropositivity in the multiple regression analysis. Males (β =-1.18; 95% CI: -1.73,-0.64) and chronic liver diseases (β =-1.45; 95% CI: -2.13, -0.76) were significantly associated with lower NAbs titers. In 26 patients with liver failure, both antibody seropositivity (53.8% vs 84.6%, p<0.05) and titer (3.55 vs 4.32 log2 AU/ml, p<0.001) did not decrease but increased after artificial liver plasmapheresis. NAbs response to COVID-19 inactivated or subunit recombinant vaccines was waning in patients with liver dysfunction. Moreover, patients with male sex, severe liver injury and chronic liver diseases have an increased risk of poor antibody responses.

Characteristics of patients with SARS-COV-2 PCR re-positivity after recovering from COVID-19.

The purpose of this study was to analyse the clinical characteristics of patients with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) PCR re-positivity after recovering from coronavirus disease 2019 (COVID-19). Patients (n = 1391) from Guangzhou, China, who had recovered from COVID-19 were recruited between 7 September 2021 and 11 March 2022. Data on epidemiology, symptoms, laboratory test results and treatment were analysed. In this study, 42.7% of recovered patients had re-positive result. Most re-positive patients were asymptomatic, did not have severe comorbidities, and were not contagious. The re-positivity rate was 39%, 46%, 11% and 25% in patients who had received inactivated, mRNA, adenovirus vector and recombinant subunit vaccines, respectively. Seven independent risk factors for testing re-positive were identified, and a predictive model was constructed using these variables. The predictors of re-positivity were COVID-19 vaccination status, previous SARs-CoV-12 infection prior to the most recent episode, renal function, SARS-CoV-2 IgG and IgM antibody levels and white blood cell count. The predictive model could benefit the control of the spread of COVID-19.

Extracellular polysaccharide of Lactobacillus plantarum enhance immune efficacy of oprH gene recombinant subunit vaccine from Pseudomonas aeruginosa.

To evaluate the immune enhancement effect of the extracellular polysaccharide of Lactobacillus plantarum on oprH recombinant subunit vaccine from Pseudomonas aeruginosa, a recombinant subunit vaccine of oprH (rOprH vaccine) was developed. The EP-rOprH vaccine was prepared with the extracellular polysaccharide of L. plantarum as an adjuvant. Mice were vaccinated with the rOprH and EP-rOprH vaccines, and the outer membrane protein (OMP) and inactivated vaccines were used as controls. The levels of serum antibody, interferon-γ (IFN-γ), interleukin (IL-2), and IL-4 were determined after vaccination. Finally, the protective efficacy of the vaccine was evaluated after challenge with virulent P. aeruginosa. Following vaccination, the serum antibody levels were significantly higher in mice vaccinated with the EP-rOprH vaccine than in those vaccinated with the rOprH vaccine (P<0.05). Moreover, the serum antibody levels detected in the EP-rOprH vaccine group were similar to those detected in the OMP vaccine group when P. aeruginosa suspension was used as the coating antigen. However, the levels in the EP-rOprH vaccine group were higher than those in the OMP vaccine and inactivated vaccine groups when the purified rOprH protein was used as the coating antigen (P<0.05). The level of IFN-γ, IL-2, and IL-4 in mice vaccinated with the EP-rOprH vaccine was significantly higher than that in mice vaccinated with the rOprH vaccine (P<0.05) and comparable to that in mice vaccinated with the OMP vaccine. The protective rates were 65%, 80%, 80%, and 95% with the rOprH, EP-rOprH, OMP, and inactivated vaccines, respectively. Thus, the extracellular polysaccharide of L. plantarum significantly enhanced the immune response and protection provided by the recombinant subunit vaccine of oprH.

Efficacy, Effectiveness, and Safety of Herpes Zoster Vaccine in Immunocompromised Patients

The varicella-zoster is a dangerous virus that has the potential to lead to many fatal conditions. People with low immune systems tend to be affected by this virus and they are more prone to HZ and its complications. This virus can't be treated with an antiviral drug as they may not respond to them. It's important to note that the live attenuated vaccine and the adjuvant recombinant subunit vaccine have different characteristics and recommended uses for individuals with compromised immune systems. This paper aims to assess these vaccines' efficacy, effectiveness, and safety in such individuals. However, autoimmune therapy may create more side effects which can be more in the injection use. In conclusion, vaccination is a measure against HZ and its complications for people with compromised immune systems. The RZV vaccine is widely regarded as the choice because it has shown effectiveness and is considered safe, for different groups of people, with weakened immune systems. For people, with slight immune-compromised, the ZVL vaccine might be a choice. However, it's crucial to assess each situation on a basis.

Recombinant Protein Mimicking the Antigenic Structure of the Viral Surface Envelope Protein Reinforces Induction of an Antigen-Specific and Virus-Neutralizing Immune Response Against Dengue Virus.

Dengue virus (DENV), belonging to the family Flaviviridae, is the causative agent of dengue and comprises four serotypes. A second heterologous DENV infection is a critical risk factor for severe dengue, and no effective vaccine is available to prevent infection by all four DENV serotypes. Recombinant DENV vaccines are primarily based on the envelope proteins, prM and E. The E protein and its envelope domain III (EDIII) have been investigated as candidate antigens (Ags) for recombinant subunit vaccines. However, most EDIII-based Ags are monomers that do not display the cognate antigenic structure of E protein, which is essential for induction of virus-neutralizing immunity. Here, we developed recombinant DENV-2 envelope domain (r2ED) protein as an Ag that mimics the quaternary structure of E protein on the DENV surface. We confirmed that r2ED retained the conformational epitope displayed at the E-dimer interface, which reportedly exhibits broad virus-neutralizing capacity, without displaying the fusion loop epitope that causes antibody (Ab)-dependent enhancement. Furthermore, compared with EDIII alone, r2ED elicited stronger Ag-specific and cross-reactive neutralizing Ab and T cell-mediated immune responses in mice. This Ag-specific immunity was maintained at an elevated level 6months after the last immunization, suggesting sustained Ag-specific immune memory. Taken together, these observations suggest that r2ED could be used to develop an improved subunit vaccine capable of inducing a broadly cross-reactive and long-lasting immune response against DENV infection.

Evaluation of the immune protective effects of rEmMIC2 and rEmMIC3 from Eimeria magna in rabbits.

Eimeria magna is a common pathogen in rabbits, which results in lethargy, weight loss, diarrhea, and even death in severe cases after infection. The current method for preventing rabbit coccidiosis is to add anticoccidial drugs to the diet. However, there are many concerns about drug resistance and drug residues. In our study, the rEmMIC2 and rEmMIC3 proteins were cloned and expressed to evaluate potential as recombinant subunit vaccine candidate antigens. The protective effects of rEmMIC2 and rEmMIC3 were evaluated by the relative weight gain ratio, oocyst decrease rate, anticoccidial index, feed conversion ratio, pathological alterations, clinical symptoms, specific IgG antibody, and cytokine levels in rabbits. The molecular weights of rEmMIC2 and rEmMIC3 were 18.69kDa and 17.47kDa, respectively. After the coccidia challenge, the control groups showed anorexia and soft poop, whereas the experimental group showed few anorexia symptoms. Significantly different from the control group, the relative weight gain ratios of the immunized rEmMIC2 and rEmMIC3 groups were 78.37% and 75.29%, respectively, and the oocyst reduction was 77.95% and 76.09%, respectively, and the anticoccidial index was 171.12 and 169.29, respectively. IgG antibody, IFN-γ, IL-4, IL-10, and IL-17 levels were significantly increased in the experimental group. The results showed that rEmMIC2 and rEmMIC3 have potential as vaccine candidate antigens.

Serum antibody profiling identifies vaccine-induced correlates of protection against aerosolized ricin toxin in rhesus macaques

Inhalation of the biothreat agent, ricin toxin (RT), provokes a localized inflammatory response associated with pulmonary congestion, edema, neutrophil infiltration, and severe acute respiratory distress. The extreme toxicity of RT is the result of the toxin’s B chain (RTB) promoting rapid uptake into alveolar macrophages and lung epithelial cells, coupled with the A chain’s (RTA) potent ribosome-inactivating properties. We previously reported that intramuscular vaccination of rhesus macaques with a lyophilized, alum-adsorbed recombinant RTA subunit vaccine (RiVax®) was sufficient to confer protection against a lethal dose of aerosolized RT. That study implicated RT-specific serum IgG, toxin-neutralizing activity (TNA), and epitope-specific responses as being associated with immunity. However, it was not possible to define actual correlates of protection (COP) because all vaccinated animals survived the RT challenge. We addressed the issue of COP in the current study, by vaccinating groups of rhesus macaques with RiVax® following the previously determined protective regimen (100 µg on study days 0, 30 and 60) or one of two anticipated suboptimal regimens (100 µg on study days 30 and 60; 35 µg on study days 0, 30, and 60). Two unvaccinated animals served as controls. The animals were challenged with ~5 × LD50s of aerosolized RT on study day 110. We report that all vaccinated animals seroconverted prior to RT challenge, with the majority also having measurable TNA, although neither antibody levels nor TNA reached statistical significance with regard to a correlation with protection. By contrast, survival correlated with pre-challenge, epitope-specific serum IgG levels, derived from a competitive sandwich ELISA using a panel of toxin-neutralizing monoclonal antibodies directed against distinct epitopes on RiVax®. The identification of a species-neutral, competitive ELISA that correlates with vaccine-induced protection against RT in nonhuman represents an important advance in the development of medical countermeasures (MCM) against a persistent biothreat.

Antibodies Induced by Homologous or Heterologous Inactivated (CoronaVac/BBIBP-CorV) and Recombinant Protein Subunit Vaccines (ZF2001) Dramatically Enhanced Inhibitory Abilities against B.1.351, B.1.617.2, and B.1.1.529 Variants.

Safe and effective vaccines for Corona Virus Disease 2019 (COVID-19) can prevent the virus from infecting human populations and treat patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we discuss the inhibitory abilities of primary and booster vaccine-induced antibodies inhibitory ability toward the SARS-CoV-2 wild-type strain, as well as B.1.1.7, B.1.351, P.1, B.1.617.2, and B.1.1.529. We confirmed these antibodies had the strongest inhibitory effects on the wild-type strain and cross-inhibition activities against other mutant strains after two inactivated vaccine doses. However, the B.1.351, B.1.617.2 and B.1.1.529 mutants exhibit antibody resistance in the vaccine serum. Antibodies induced by homologous inactivated vaccines (n = 92) presented more effective inhibition against tested SARS-CoV-2 strains (p &lt; 0.0001), especially B.1.351, B.1.617.2, and B.1.1.529 mutant strains, which had strong immune escape characteristics. In addition, a heterologous booster vaccination (n = 50) of a protein subunit vaccine ZifiVax (ZF2001) significantly restored humoral immune responses and even showed an increasing response against wild-type, B.1.351, B.1.617.2, and B.1.1.529 than homologous inactivated vaccines. Our analysis of the humoral immune response elicited by the different vaccine regimens, including inhibiting antibodies, indicated that a booster, whether homologous or heterologous, could be essential for achieving greater efficacy against SARS-CoV-2.

A therapeutic vaccine strategy to prevent Pneumocystis pneumonia in an immunocompromised host in a non-human primate model of HIV and Pneumocystis co-infection.

Pneumocystis is a ubiquitous fungal pathogen that causes pneumonia (PCP) and pulmonary sequelae in HIV-infected individuals and other immunocompromised populations. With the success of anti-retroviral therapy for HIV-infected individuals the frequency of PCP in that population has decreased, however, PCP remains a significant cause of morbidity and mortality in individuals with hematologic and solid malignancies, and in individuals treated with immunosuppressive therapies for autoimmune diseases, and following bone marrow and solid organ transplantation. Despite the clinical need, there is no approved vaccine to prevent PCP in vulnerable populations. The ultimate goal of the field is to develop an effective vaccine that can overcome immune deficits in at risk populations and induce long-lasting protective immunity to Pneumocystis. Toward this goal, our laboratory has established a model of PCP co-infection in simian immunodeficiency virus (SIV)-infected non-human primates (NHP) and identified a recombinant protein sub-unit vaccine, KEX1, that induces robust anti-Pneumocystis immunity in immune-competent macaques that is durable and prevents PCP following simian immunodeficiency virus (SIV)-induced immunosuppression. Type I, or invariant natural killer T (iNKT) cells have the potential to provide B cell help under conditions of reduced CD4+ T cell help. In the present study, we used the SIV model of HIV infection to address whether therapeutic vaccination with the iNKT cell-activating adjuvant α-galactosylceramide (α-GC) and KEX1 (α-GC+KEX1) can effectively boost anti-Pneumocystis humoral immunity following virus-induced immunosuppression. Immunization of antigen-experienced NHPs with α-GC+KEX1 during the early chronic phase of SIV-infection significantly boosted anti-Pneumocystis humoral immunity by increasing memory B cells and antibody titers, and enhanced titer durability during SIV-induced immunosuppression. This therapeutic vaccination strategy boosted anti-Pneumocystis immune responses during SIV-infection and contributed to protection against Pneumocystis co-infection in KEX1-vaccinated macaques. These studies present a novel strategy for stimulating durable anti-Pneumocystis humoral immunity in the context of complex, chronic SIV-induced immunosuppression and may be further applied to immunization of other immunosuppressed populations, and toward other common recall antigens.

Current progress in the development of prophylactic and therapeutic vaccines.

Vaccines are essential public health tools and play an important role in reducing the burden of infectious diseases in the population. Emerging infectious diseases and outbreaks pose new challenges for vaccine development, requiring the rapid design and production of safe and effective vaccines against diseases with limited resources. Here, we focus on the development of vaccines in broad fields ranging from conventional prophylactic vaccines against infectious diseases to therapeutic vaccines against chronic diseases and cancer providing a comprehensive overview of recent advances in eight different vaccine forms (live attenuated vaccines, inactivated vaccines, polysaccharide and polysaccharide conjugate vaccines, recombinant subunit vaccines, virus-like particle and nanoparticle vaccines, polypeptide vaccines, DNA vaccines, and mRNA vaccines) and the therapeutic vaccines against five solid tumors (lung cancer breast cancer colorectal cancer liver cancer and gastric cancer), three infectious diseases (human immunodeficiency virus, hepatitis B virus and human papillomavirus-induced diseases) and three common chronic diseases (hypertension, diabetes mellitus and dyslipidemia). We aim to provide new insights into vaccine technologies, platforms, applications and understanding of potential next-generation preventive and therapeutic vaccine technologies paving the way for the vaccines design in the future.

Mixed formulation of mRNA and protein-based COVID-19 vaccines triggered superior neutralizing antibody responses.

Integrating different types of vaccines into a singular immunization regimen is an effective and accessible approach to strengthen and broaden the immunogenicity of existing coronavirus disease 2019 (COVID-19) vaccine candidates. To optimize the immunization strategy of the novel mRNA-based vaccine and recombinant protein subunit vaccine that attracted much attention in COVID-19 vaccine development, we evaluated the immunogenicity of different combined regimens with the mRNA vaccine (RNA-RBD) and protein subunit vaccine (PS-RBD) in mice. Compared with homologous immunization of RNA-RBD or PS-RBD, heterologous prime-boost strategies for mRNA and protein subunit vaccines failed to simultaneously enhance neutralizing antibody (NAb) and Th1 cellular response in this study, showing modestly higher serum neutralizing activity and antibody-dependent cell-mediated cytotoxicity for "PS-RBD prime, RNA-RBD boost" and robust Th1 type cellular response for "RNA-RBD prime, PS-RBD boost". Interestingly, immunizing the mice with the mixed formulation of the two aforementioned vaccines in various proportions further significantly enhanced the NAb responses against ancestral, Delta, and Omicron strains and manifested increased Th1-type responses, suggesting that a mixed formulation of mRNA and protein vaccines might be a more prospective vaccination strategy. This study provides basic research data on the combined vaccination strategies of mRNA and protein-based COVID-19 vaccines.