Vaccine最新文献

The TLR4 (Toll-like receptor 4)-activating agonist MPLA (monophosphoryl lipid A) is a key component of the adjuvant systems AS01 and AS04, utilized in marketed preventive vaccines for several infectious pathogens. As MPLA is a biologically-derived product containing a mixture of several lipid A congeners with a 4' phosphoryl group and varying numbers of acyl chains with distinct activities, extensive efforts to refine its production and immunogenicity are ongoing; notably, the development of the BECC (Bacterial Enzymatic Combinatorial Chemistry) system in which bacteria express lipid A-modifying enzymes to produce a panoply of lipid A congeners. In an effort to characterize the adjuvant activity of these lipid A congeners, we compared biologically-derived and synthetic versions of BECC470 and BECC438 for adjuvant activity in BALB/c mice vaccinated with the HPV (Human papilloma virus) VLP-based vaccine, RG1-VLP. Synthetic BECC compounds compared favorably to biological versions and, in the case of synthetic BECC470, were routinely superior to their biologically-derived BECC counterpart. Synthetic BECC470-adjuvanted vaccines achieved broad spectrum immune activity characterized by elevated levels of total IgG and IgG2a subtype specific to HPV16 L1 VLPs and the HPV16 L2 peptide, as well as robust HPV16-neutralizing antibody titers. In addition, synthetic BECC470 promoted strong T cell responses to HPV16 L1, increased memory B cell frequency, and increased the T follicular helper cell (Tfh) population in draining lymph nodes. In contrast, the biologically-derived form of BECC470 induced an immune profile specific for highest levels of HPV16 L2-specific IgG2a as well as antibodies cross-neutralizing to HPV18 and HPV39. These data confirm that a synthetically-derived BECC compound can be combined with Alhydrogel to adjuvant the RG1-VLP vaccine as can biologically-derived BECC compounds and MPLA, albeit with subtly distinct immune responses. The distinctions in immune profiles triggered by these BECC compounds warrant further exploration for their capacity to activate TLR4 and modulate immune responses to vaccines.

Epidemiological studies suggest that heterogeneity in influenza vaccine antibody response can be associated with specific host factors, including pre-vaccination immune status, age, gender, and vaccination history. However, the pattern of reported associations varies between studies. To better understand the underlying influences on antibody responses, we combined host factors and vaccine-induced in-host antibody kinetics from a cohort study conducted across multiple seasons with a unified analysis framework. We developed a flexible individual-level Bayesian model to estimate associations and interactions between host factors, including pre-vaccine HAI titre, age, sex, vaccination history and study setting, and vaccine-induced HAI titre antibody boosting and waning. We applied the model to derive population-level and individual effects of post-vaccine antibody kinetics for A(H1N1) and A(H3N2) influenza subtypes. We found that post-vaccine HAI titre dynamics were significantly influenced by pre-vaccination HAI titre and vaccination history and that lower pre-vaccination HAI titre results in longer durations of seroprotection (HAI titre equal to 1:40 or higher). We also observed that the effect of vaccination history on antibody boosting was stronger for egg-grown A(H1N1) vaccinating strains in individuals with higher pre-vaccination HAI titres, whereas this effect diminished for egg-grown A(H3N2) vaccinating strains. Consequently, for cell-grown A(H1N1), our inference finds that the expected duration of seroprotection post-vaccination was 171 (95 % Posterior Predictive Interval[PPI] 128-220) and 159 (95 % PPI 120-200) days longer for those who are infrequently vaccinated (<2 vaccines in last five years) compared to those who are frequently vaccinated (2 or more vaccines in the last five years) at pre-vaccination HAI titre values of 1:10 and 1:20 respectively. In addition, we found significant differences in the empirical distributions that describe the individual-level duration of seroprotection for A(H1N1) cell-grown strains. In future, studies that rely on serological endpoints should include the impact of pre-vaccine HAI titre and prior vaccination status on seropositivity and seroconversion estimates, as these can significantly influence an individual's post-vaccination antibody kinetics.

Vaccine hesitancy fueled by ignorance, negativity, and false information on social media affects public health globally. Brazil's decline in vaccination, influenced by denialism and misinformation, increases the risk of polio reintroduction in Latin America. Combatting scientific Fake News is crucial to prevent irreversible consequences to public health.

Background: In 2014, the Advisory Committee on Immunization Practices recommended routine use of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults age ≥ 65 years. Incidence of most PCV13-serotype cases declined, however serotype 3 cases have persisted. We estimated PCV13 vaccine effectiveness (VE) against PCV13-serotypes and serotype 3 invasive pneumococcal disease (IPD) among Kaiser Permanente Northern California (KPNC) adults.

Methods: This observational study included adults ≥65 years between September 1, 2014-December 31, 2020. We used active laboratory-based surveillance to identify and serotype all Streptococcus pneumoniae isolates obtained from normally-sterile sites. We estimated the odds ratio (OR) of vaccine-type IPD using conditional logistic regression stratified by age and calendar day, adjusting for sex, age, race, ethnicity, influenza vaccine receipt, 23-valent pneumococcal polysaccharide vaccine receipt since age 65, pneumonia risk factors, healthcare utilization, and KPNC service area. We estimated VE_Adjusted as (1-OR_Adjusted) × 100 %.

Results: There were 610,576 adults ≥65 years in the study population. By the end of the study period, PCV13 coverage was nearly 80 %. There were 307 IPD cases during the study period, of which 98 (31.9 %) were serotype 3. PCV13 was associated with a VE_Adjusted of 61.5 % (95 % CI: 36.2, 76.7; p < 0.001) against PCV13-serotype IPD and 46.3 % (95 % CI: -2.4, 77.9; p = 0.06) against serotype 3 IPD.

Conclusions: PCV13 vaccination protected adults ≥65 years against IPD due to PCV13 serotypes. Continued surveillance will be critical in the ≥65-year-old population to assess the impact of higher valent PCVs on IPD serotype distribution, including individual serotypes such as serotype 3.

Background: The childhood immunization coverage in Serbian communities in Kosovo after the 1999 armed conflict has not been investigated. The study purpose was to evaluate the trend of immunization coverage with vaccines from the national childhood immunization program in Serbian communities in Kosovo and Metohija from 2003 to 2022.

Methods: Data were retrieved from the annual reports of the Public Health Institute of Kosovska Mitrovica received through notifications from the primary health centers where vaccines are being administered. Data were analyzed using the linear regression and join-point regression models.

Results: In the examined period, a significant decrease in vaccination coverage was observed for the following diseases: diphtheria, tetanus and pertussis (DTP), polio, as well as measles, mumps and rubella vaccines (MMR), then, the first revaccination for DTP and polio, the second revaccination against diphtheria and tetanus for children (DT) and polio, and the third revaccination against diphtheria and tetanus for adults (dT), as well as the second dose of the MMR vaccine. During the COVID-19 pandemic, a significant decrease in coverage was observed for primary vaccination against: DTP, polio and hepatitis B, first and second doses of the MMR vaccine, as well as the first and second revaccination for DTP and polio, and the third revaccination for dT.

Conclusion: A decline in coverage with DTP, MMR, polio and hepatitis B vaccines was observed between 2003 and 2022. This was even more pronounced during the COVID-19 pandemic. Further research on individual-level factors contributing to lower vaccination coverage is warranted.

Diseases caused by Streptococcus pneumoniae (pneumococcus) produce a great impact on public health, killing about one million people annually despite available vaccines. Recent research has revealed that the pneumococcus produces extracellular vesicles (pEVs), which display selective cargo and hold potential for vaccine development. Here, we evaluated the immunogenicity and protective potential of pEVs derived from a non-encapsulated pneumococcal strain (R6) using murine models of pneumococcal colonization and invasive pneumonia. Characterization of the immune response revealed that while pEVs contain multiple virulence determinants, immunization with these nanoparticles only induces antibodies against a subset of them. Specifically, subcutaneous immunization elicits a high antibody response against PspA, a modest response against PrsA, and limited response against Ply, MalX and PsaA. The antibody response was further supported by agglutination studies, showing that sera from pEV immunized mice agglutinate pneumococci and that PspA contributes to this response in a strain-dependent manner. Subcutaneous immunization with pEVs provides protection in the invasive pneumonia model whereas nasal immunization results in one log reduction in pneumococcal colonization of the upper respiratory tract. Finally, PspA is a strong contributor to protection in the invasive model and provides a degree of protection even across heterologous families of PspA. We conclude that pEVs demonstrate potential for vaccine development, protecting across capsular types and providing some degree of protection across heterologous PspA variants.