Vaccines最新文献

Background: The COVID-19 pandemic has led to the rapid development of new vaccines and methods of testing vaccine-induced immunity. Despite the extensive research that has been conducted on the level of specific antibodies, less attention has been paid to studying the avidity of these antibodies. The avidity of serum antibodies is associated with a vaccine showing high effectiveness and reflects the process of affinity maturation. In the context of vaccines against SARS-CoV-2, only a limited number of studies have investigated the avidity of antibodies, often solely focusing on the wild-type virus following vaccination. This study provides new insights into the avidity of serum antibodies following adenovirus-based boosters. We focused on the effects of an intranasal Salnavac booster, which is compared, using a single analytical platform, to an intramuscular Sputnik V.

Methods: The avidity of RBD-specific IgGs and IgAs was investigated through ELISA using urea and biolayer interferometry.

Results: The results demonstrated the similar avidities of serum antibodies, which were induced by both vaccines for six months post-booster. However, an increase in antibody avidity was observed for the wild-type and Delta variants, but not for the BA.4/5 variant.

Conclusions: Collectively, our data provide the insights into antibody avidity maturation after the adenovirus-based vaccines against SARS-CoV-2.

Plague, caused by Yersinia pestis, poses a public health threat not only due to sporadic outbreaks across the globe but also due to its potential as a biothreat agent. Ironically, among the seven deadliest pandemics in global history, three were caused by Y. pestis. Pneumonic plague, the more contagious and severe form of the disease, is difficult to contain, requiring either prophylactic antibiotic treatment or vaccination. However, no vaccine (live attenuated or subunit) is currently approved by the Food and Drug Administration, requiring rigorous preclinical studies in different animal models, thus forming the basis of this study. Objectives: The aim of this study was to evaluate the efficacy and immune responses of two live attenuated vaccines (LAVs), LMA and LMP, either alone or in combination with a trivalent adenoviral vector-based vaccine (Ad5-YFV), in IL-17A-depleted and IgG control mice by using an anti-IL-17A monoclonal antibody (mAb) or its matched isotype IgG, respectively. Methods: IL-17A mAb or IgG isotype control was administered to mice twice per week to their respective groups during the course of immunization. Serum, spleens, and broncho-alveolar lavage fluid (BALF) were collected for assessing immunological responses, and another cohort of mice was intranasally challenged with a lethal dose of parental Y. pestis CO92. Results: Robust humoral and cellular immune responses followed by complete protection were observed in all vaccinated animals against highly lethal intranasal challenge doses of parental Y. pestis CO92. Serum IgG titers to YscF and overall mucosal IgA titers to all three antigens of the Ad5-YFV vaccine were significantly lower, with slightly reduced serum LcrV-neutralizing antibodies when IL-17A was depleted compared to IgG control animals during the course of immunization. A remarkable reduction in Th1 (IFNγ or IL-2) and Th17 cell populations was observed in IL-17A-depleted mice compared to IgG controls in response to vaccination. On the other hand, B cell activities in germinal centers, overall activated antigen-specific T cells, and memory B and T cells remained at comparable levels in both vaccinated IL-17A-depleted and IgG control mice. Conclusions: These data demonstrated the effectiveness of our vaccines even under the reduced levels of both Th1 and Th17 responses and thus should be suitable for those individuals associated with certain immune deficiencies.

Background/Objectives:Clostridium perfringens is a common opportunistic pathogen that causes gastrointestinal diseases in livestock and poultry. Our preliminary research has demonstrated that administering oral yeast-cell microcapsule (YCM)-mediated DNA vaccines can effectively stimulate mucosal immunity, thereby preventing the occurrence of gastrointestinal diseases. Methods: In this study, the C. perfringens α-toxin gene was first cloned and the H126G and C-terminal (C247-370) mutations were created. The corresponding DNA vaccine cassettes driven by a CMV promoter were constructed and were cloned into a yeast shuttle vector. Recombinant yeast strains transformed with these shuttle vectors were then prepared as the YCMs for the subsequent oral immunization of mice. Results: Oral administration of recombinant YCMs can induce an effective immune response, and the H126G YCM performed much better than C247-370. Further evidence suggested that YCM administration may contribute to modulating the gut environment by altering gut microbiota and enhancing bacterial richness. Conclusions: Our study indicated that the oral administration of YCM-mediated DNA vaccines can induce effective intestinal immunity and may also alter the composition of the gut microbiota, suggesting a promising candidate vaccine strategy against C. perfringens-induced animal diseases.

Background: A vaccination programme against severe acute respiratory syndrome coronavirus 2 was initiated in Portugal in December 2020. In this study, we report the findings of a prospective cohort study implemented with the objective of monitoring antibody production in response to COVID-19 vaccination. Methods: The humoral immune response to vaccination was followed up using blood samples collected from 191 healthcare workers. Participants were split into three groups: the Oxford-AstraZeneca (Vaxzevria) vaccine group (n = 68), the Pfizer-BioNTech COVID-19 (Comirnaty) vaccine group (n = 51), and the Post-COVID group (n = 72). The kinetics of anti-spike antibody production were evaluated until 56 days on average after the third dose (booster). Results: We observed that antibody titres peaked approximately one month after full vaccination and declined steadily thereafter. We also found that mRNA vaccination induces higher titres of antibodies than viral vector vaccination, and both generate greater antibody responses than mild or moderate COVID-19. Additionally, whilst the booster for the Oxford-AstraZeneca and Pfizer-BioNTech groups led to antibody levels higher than those at any previous sample collection point, the booster for the Post-COVID group (persons with a history of COVID-19 prior to vaccination) led to antibody levels lower than those attained one month after the second dose. Interpretation: Our results indicate that there are different kinetics of antibody production between individuals who received the Pfizer-BioNtech mRNA vaccine and those who received the Oxford-AstraZeneca vector vaccine, or individuals who had COVID-19 before being vaccinated. Additionally, we observed that exposure to either natural infection or vaccination modulates the response to subsequent vaccination. This is particularly evident after administration of the third dose to the Post-COVID group, where our findings point to a hindrance in vaccine boosting, probably due to unwanted feedback by high titres of pre-existing antibodies.

Background/objectives: Although the protective effects of zinc against COVID-19 are documented, its impact on COVID-19 vaccine immunogenicity remains unknown.

Methods: We conducted a prospective study involving a cohort of 79 Japanese individuals (aged 21-56 years; comprising three subcohorts) and measured their serum zinc levels pre-vaccination and anti-SARS-CoV-2 IgM/IgG levels pre- and post-vaccination over 4 months.

Results: Serum zinc concentrations ranged between 74-140 and 64-113 μg/dL in male and female individuals, respectively, with one male and 11 female participants exhibiting subclinical zinc deficiency (60-80 μg/dL). Mixed models for antibody titers, accounting for the subcohorts, repeat measurements, and covariates (e.g., vaccine type, sex, age, height, steroid use, medical history, smoking and drinking habits, perceived stress, and sleep disturbances) showed positive effects of zinc on IgM (p = 0.012) and IgG (p = 0.013) in 45 female individuals with 255 observations. However, a similar association was not found in the 34 male participants with 162 observations. This discrepancy may be attributed to one participant being included in the subcohort with frequent repeat measurements (10 repeats in 4 months). COVID-19 mRNA vaccine immunogenicity was enhanced in the participants with high baseline blood zinc levels within the reference range.

Conclusions: Our findings underscore the relevance of maintaining adequate zinc levels before vaccination, which can be achieved through a balanced diet and healthy lifestyle choices.

Background: Cervical cancer is associated with persistent infection of high-risk human papillomaviruses (HPVs). Prophylactic HPV vaccines have been recommended and have significant efficacy in preventing cervical cancer. Multivalent HPV vaccines have a better preventative effect on HPV-related diseases. However, there is currently only one nine-valent HPV vaccine on the market: Gardasil^® 9. The development of new HPV vaccines is still urgent in order to achieve the goal of eliminating cervical cancer as proposed by the WHO.

Methods: In this study, we developed a nine-valent recombinant HPV virus-like particle (VLP) vaccine (HPV-9 vaccine) containing HPV type 6, 11, 16, 18, 31, 33, 45, 52, and 58 antigens, with an adjuvant of aluminum phosphate (AlPO₄). The type-specific L1 proteins were recombinantly expressed using Pichia pastoris, followed by self-assembly into VLPs. Immunogenicity studies of the HPV-9 vaccine were performed using rodents (mice and rats) and non-human primates (macaques) as animal models.

Results: Immunogenicity studies showed that the HPV-9 vaccine is able to elicit a robust and long-lasting neutralizing antibody response in rodents (mice and rats) and non-human primates (cynomolgus macaque) models. The HPV-9 vaccine shows immunogenicity comparable to that of Walrinvax^® and Gardasil^® 9.

Conclusions: In summary, this study provides a comprehensive investigation of the immunogenicity of the HPV-9 vaccine, including its immune persistence. These findings, derived from using models of diverse animal species, contribute valuable insights into the potential efficacy of the vaccine candidate in clinical settings.

Background/Objectives: IgA1 protease is one of the virulence factors of Neisseria meningitidis, Haemophilus influenzae and other pathogens causing bacterial meningitis. The aim of this research is to create recombinant proteins based on fragments of the mature IgA1 protease A²⁸-P¹⁰⁰⁴ from N. meningitidis serogroup B strain H44/76. These proteins are potential components of an antimeningococcal vaccine for protection against infections caused by pathogenic strains of N. meningitidis and other bacteria producing serine-type IgA1 proteases. Methods: To obtain promising antigens for creating a vaccine, we designed and obtained several recombinant proteins. These proteins consisted of single or directly connected fragments selected from various regions of the IgA1 protease A²⁸-P¹⁰⁰⁴. The choice of these fragments was based on our calculated data on the distribution of linear and conformational B-cell epitopes and MHC-II T-cell epitopes in the structure of IgA1 protease, taking into account the physicochemical properties of potential compounds and the results of a comparative analysis of the spatial structures of the original IgA1 protease and potential recombinant proteins. We studied the immunogenic and protective effects of the obtained proteins on the BALB/c mice against meningococci of serogroups A, B and C. Results: Proteins MA²⁸-P¹⁰⁰⁴-LEH₆, MW¹⁴⁰-K⁸³³-LEH₆, MW³²⁹-P¹⁰⁰⁴-LEH₆, M(W¹⁴⁰-H³²⁸)-(W⁴¹²-D⁶⁰⁴)-(Y⁸⁶⁶-P¹⁰⁰⁴)-LEH₆ and M(W¹⁴⁰-Q²⁹⁹)-(Y⁸⁶⁶-P¹⁰⁰⁴)-LEH₆ have shown the following antibody titers, 10³/titer: 11 ± 1, 6 ± 2, 6 ± 1, 9 ± 1 and 22 ± 3, respectively. Also, the last two proteins have shown the best average degree of protection from N. meningitidis serogroups A, B and C, %: 62 ± 6, 63 ± 5, 67 ± 4 respectively for M(W¹⁴⁰-H³²⁸)-(W⁴¹²-D⁶⁰⁴)-(Y⁸⁶⁶-P¹⁰⁰⁴)-LEH₆ and 70 ± 5, 66 ± 6, 83 ± 3 respectively for M(W¹⁴⁰-Q²⁹⁹)-(Y⁸⁶⁶-P¹⁰⁰⁴)-LEH₆. Conclusions: We selected two recombinant proteins consisting of two (M(W¹⁴⁰-Q²⁹⁹)-(Y⁸⁶⁶-P¹⁰⁰⁴)-LEH₆) or three (M(W¹⁴⁰-H³²⁸)-(W⁴¹²-D⁶⁰⁴)-(Y⁸⁶⁶-P¹⁰⁰⁴)-LEH₆) linked fragments of IgA1 protease A²⁸-P¹⁰⁰⁴ as candidate active component for an antimeningococcal vaccine.

Background: Duck adenovirus 3 (DAdV-3) is an emerging pathogen that has caused severe economic losses to the duck industry in China. Recently, the infection of ducks with serotype 4 fowl adenovirus (FAdV-4) has also been reported in China. Therefore, an efficient bivalent vaccine to control the diseases caused by DAdV-3 and FAdV-4 is extremely urgent. In our previous study, a recombinant FAdV-4 expressing Fiber-2 of DAdV-3 was generated and designated as rFAdV-4-Fiber-2/DAdV-3.

Methods: Here, the recombinant virus rFAdV-4-Fiber-2/DAdV-3 was inactivated to serve as a bivalent vaccine, and its immunogenicity and protective efficacy against DAdV-3 were evaluated in Muscovy ducks.

Results: The subcutaneous injection of rFAdV-4-Fiber-2/DAdV-3 could efficiently induce antibodies against Fiber-2 of DAdV-3 and neutralize antibodies against FAdV-4. After challenges with DAdV-3, in comparison with the non-immunized ducks, the immunized ducks did not show any bodyweight loss, gross lesions, or histopathologic change. Moreover, viral loads in livers and kidneys from immunized ducks were undetectable, whereas those in non-immunized ducks with challenge were significantly high.

Conclusions: All these data demonstrate that the inactivated recombinant virus rFAdV-4-Fiber-2/DAdV-3 has the potential to be an efficient vaccine candidate against both FAdV-4 and DAdV-3, although efficacy for FAdV-4 needs to be confirmed experimentally.

Background/Objectives: Respiratory syncytial virus (RSV) causes symptoms similar to a mild cold for adults, but in case of infants, it causes bronchitis and/or pneumonia, and in some cases, mortality. Mucosal immunity within the respiratory tract includes tissue-resident memory T (T_RM) cells and tissue-resident memory B (B_RM) cells, which provides rapid and efficient protection against RSV re-infection. Therefore, vaccine strategies should aim to generate mucosal immune responses. However, the interactions between RSV vaccines and mucosal immune responses within the respiratory tract are poorly understood. We evaluated a mucosal immune system following immunization by RSV vaccine with poly-sorbitol transporter (RSV-PST), a nanoparticle adjuvant. Methods: We intranasally immunized the RSV-PST and identified the systemic and mucosal immune responses. Furthermore, we challenged with RSV A2 strain after immunization and investigated the protective effects. Results: Consequently, antigen-specific CD8⁺ T_RM cells were markedly elevated in the lung parenchyma, yet exhibited impaired cytokine expression. In contrast, humoral immunity, with systemic antibody production from serum, but not in the respiratory tract, was significantly increased by RSV-PST immunization. Interestingly, the production of respiratory mucosal antigen-specific IgG after RSV A2 challenge dramatically increased in the bronchoalveolar lavage fluid (BALF) of the RSV-PST immunized group in the presence of FTY720, and the lung-infected RSV titer was significantly lower in this group. Furthermore, after RSV A2 challenge, CD69⁺ IgG⁺ B_RM cells were significantly increased in lung tissues in the RSV-PST group. Conclusions: The RSV-PST vaccine has protective effects against RSV infection by promoting both systemic and local humoral immunity rather than cellular immunity.

Background: Uganda's Integrated Child Health Day (ICHD) initiative aims to improve children's access to vaccinations. Although widely used as a catch-up vaccination strategy, the effectiveness of the ICHD program in increasing immunization coverage, especially among vulnerable populations, has not been recently evaluated. This study assessed the reach and uptake of ICHD for immunizations in Uganda. Methods: A mixed-methods evaluation was conducted in three districts (Rakai, Kayunga, and Bukedea) where ICHDs occurred. The data collection included a cross-sectional household survey using validated WHO-adapted questionnaires of 1432 caregivers of children under five years old, key informant interviews with 42 health managers and workers, and nine focus group discussions with caregivers between October and December 2022. The vaccines assessed were Bacillus Calmette-Guerin, oral polio, Pentavalent, pneumococcal conjugate, rotavirus (RV), and measles-rubella (MR). Results: The immunization coverage based on child health cards was over 90% for all vaccines except for the second dose of RV (88.3%) and MR (16.2%). Among the children, 2.3% had received no Pentavalent vaccine, and 69.4% were fully vaccinated for their age. Of the 631 children who attended ICHDs, 79.4% received at least one vaccine during the event. Village Health Teams (49%), health workers (18.3%), and megaphone outreach (17.9%) were the primary information sources. Key informants cited challenges with coordination, vaccine delivery, and mobilization. Conclusions: Despite operational challenges, ICHDs appear to have contributed to routine childhood vaccinations. Further research is needed to assess the sustainability and cost-effectiveness of the program.