NPJ Vaccines最新文献

The impact of adjuvants on malaria vaccine-induced antibody repertoire is poorly understood. Here, we characterize the impact of two adjuvants, Alhydrogel® and AS01, on antibody clonotype diversity, binding and function, post malaria vaccination. We expressed 132 recombinant anti-Pfs230D1 human monoclonal antibodies (mAbs) from participants immunized with malaria transmission-blocking vaccine Pfs230D1, formulated with either Alhydrogel® or AS01. Anti-Pfs230D1 mAbs generated by Alhydrogel® formulation showed higher binding frequency to Pfs230D1 compared to AS01 formulation, although the frequency of functional mAbs was similar between adjuvant groups. Overall, the AS01 formulation induced anti-Pfs230D1 functional antibodies from a broader array of germline sequences versus the Alhydrogel® formulation. All mAbs using IGHV1-69 gene from the Alhydrogel® cohort bound to recombinant Pfs230D1, but did not block parasite transmission to mosquitoes, similar to the IGHV1-69 mAbs isolated from the AS01 cohort. These findings may help inform vaccine design and adjuvant selection for immunization with Plasmodium antigens.

Since 2021, the emergence of variants of concern (VOC) has led Brazil to experience record numbers of in COVID-19 cases and deaths. The expanded spread of the SARS-CoV-2 combined with a low vaccination rate has contributed to the emergence of new mutations that may enhance viral fitness, leading to the persistence of the disease. Due to limitations in the real-time genomic monitoring of new variants in some Brazilian states, we aimed to investigate whether genomic surveillance, coupled with epidemiological data and SARS-CoV-2 variants spatiotemporal spread in a smaller region, can reflect the pandemic progression at a national level. Our findings revealed three SARS-CoV-2 variant replacements from 2021 to early 2022, corresponding to the introduction and increase in the frequency of Gamma, Delta, and Omicron variants, as indicated by peaks of the Effective Reproductive Number (Reff). These distinct clade replacements triggered two waves of COVID-19 cases, influenced by the increasing vaccine uptake over time. Our results indicated that the effectiveness of vaccination in preventing new cases during the Delta and Omicron circulations was six and eleven times higher, respectively, than during the period when Gamma was predominant, and it was highly efficient in reducing the number of deaths. Furthermore, we demonstrated that genomic monitoring at a local level can reflect the national trends in the spread and evolution of SARS-CoV-2.

Lassa fever virus (LASV), a member of the Arenavirus family, is the etiological agent of Lassa fever, a severe hemorrhagic disease that causes considerable morbidity and mortality in the endemic areas of West Africa. LASV is a rodent-borne CDC Tier One biological threat agent and is on the World Health Organization's (WHO) Priority Pathogen list. Currently, no FDA-licensed vaccines or specific therapeutics are available. Here, we describe the efficacy of a deactivated rabies virus (RABV)-based vaccine encoding the glycoprotein precursor (GPC) of LASV (LASSARAB). Nonhuman primates (NHPs) were administered a two-dose regimen of LASSARAB or an irrelevant RABV-based vaccine to serve as a negative control. NHPs immunized with LASSARAB developed strong humoral responses to LASV-GPC. Upon challenge, NHPs vaccinated with LASSARAB survived to the study endpoint, whereas NHPs in the control group did not. This study demonstrates that LASSARAB is a worthy candidate for continued development.

Lot release testing of diphtheria, tetanus and acellular pertussis vaccines traditionally relied on in vivo protection models involving challenge of laboratory animals with toxins. Meanwhile, many labs have switched to serological testing of these vaccines, which is often performed in separate in vivo assays, even if all components were formulated into one vaccine product. Here we describe the results of simultaneous serological potency determination of diphtheria (D), tetanus (T) and acellular pertussis (aP) antigens obtained following immunization of guinea pigs with multicomponent pediatric and booster vaccines from different manufacturers. The 4th World Health Organization (WHO) International Standard (IS) for diphtheria toxoid (No. 07/216) and the 4th WHO IS for tetanus toxoid (No. 08/218) were used as reference preparations. For aP, a pediatric vaccine batch containing the antigens pertussis toxoid, filamentous hemagglutinin, pertactin and fimbriae proteins type 2/3 was established as internal control. Quantification of IgG against D, T and aP antigens in guinea pig sera was performed using a hexaplex electrochemiluminescence immunoassay. We further provide proof-of-concept using experimental vaccine samples lacking or containing reduced amounts of diphtheria toxoid in the presence of full amounts of tetanus and pertussis antigens and alum adjuvant. Importantly, the assay confirmed dose-response relationships for all antigens tested and was able to detect diphtheria out-of-specification batches. The results confirmed the suitability of the protocol for combined serology batch release testing of DTaP combination vaccines as first measure towards implementation of full in vitro testing of DTaP vaccines. This report summarizes the data and the protocol used for validation prior to implementation of this method in routine batch release testing of DTaP vaccines, which led to replacement of in vivo challenge experiments in our laboratory following the 3 R (replace, reduce, refine) principle.

Tick-borne encephalitis virus (TBEV) vaccine breakthrough (VBT) infections are not uncommon in endemic areas. The clinical and immunological outcomes have been poorly investigated. We assessed the magnitude and specificity of virus-specific antibody and T cell responses after TBE in previously vaccinated subjects and compared the results with those of unvaccinated TBE patients and study subjects that received vaccination without VBT infection. Symptomatic TBEV infection of unvaccinated study subjects induced virus-specific antibody responses to the E protein and non-structural protein 1 (NS1) as well as T cell responses to structural and other non-structural (NS) proteins. After VBT infections, significantly impaired NS1-specific antibody responses were observed, while the virus-specific T cell responses to the NS proteins were relatively strong. VBT infection caused predominantly moderate to severe disease during hospitalization. The level of TBEV EDIII- and NS1-specific antibodies in unvaccinated convalescent patients inversely correlated with TBE severity and neurological symptoms early after infection.

A randomized, active-controlled, double-blind, first-in-human, phase 1 study was conducted in healthy Korean adults to evaluate the safety, tolerability, and immunogenicity of EuNmCV-5, a new pentavalent meningococcal vaccine targeting serogroups A, C, W, X, and Y. Sixty participants randomly received a single dose of either EuNmCV-5 or MenACWY-CRM, a quadrivalent vaccine containing serogroups A, C, W, and Y. Safety was assessed through monitoring anaphylactic reactions, adverse events for 28 days, and serious adverse events over 180 days. Immunogenicity was assessed via rabbit complement-dependent serum bactericidal antibody (rSBA) assay. EuNmCV-5 was safe, well-tolerated, and elicited a substantial antibody titer increase. The seroprotection rates exceeded 96.7%, and the seroconversion rates were over 85% for all the targeted serogroups. It showed higher seroconversion rates against serogroups A and C (p = 0.0016 and 0.0237, respectively) and elicited a substantial increase in GMT for all targeted serogroups compared to the MenACWY-CRM.ClinicalTrials.gov identifier: NCT05739292.

In 2022, the Australian Government listed the koala as endangered in several states due to habitat destruction, traffic strikes, dog attacks, and Chlamydia pecorum disease. This study evaluates a 10-year assessment of a Major Outer Membrane Protein-based vaccine's effectiveness against chlamydial disease in wild koalas from Southeast Queensland. Over a decade, 680 koalas were tracked, with five vaccine trials involving 165 koalas. While prior studies only offered up to two years of data, this study's extended period allowed a thorough evaluation of vaccine efficacy. Results showed that vaccinated koalas had significantly lower disease incidence, with a 64% reduction in chlamydial mortality. This vaccine demonstrated positive impacts on both male and female koalas, highlighting its crucial role in conserving the Australian koala population and mitigating the threats they face.

Avian influenza poses a severe threat to poultry production and global food security, prompting the development of vaccination programs in numerous countries. Modified live virus (MLV) vaccines, with their potential for mass application, offer a distinct advantage over existing options. However, concerns surrounding reversion, recombination, and unintended transmission have hindered the progress of MLV development for avian influenza in poultry. To address these concerns, we engineered reassortment-impaired, non-transmissible, safe, immunogenic, and protective MLVs through the rearrangement of internal gene segments and additional modifications to the surface gene segments HA and NA. The unique peptide marker aspartic acid-arginine-proline-alanine-valine-isoleucine-alanine-asparragine (DRPAVIAN) was incorporated into HA, while NA was modified to encode the chicken interleukin-18 (ckIL18) gene (MLV-H9N2-IL). In vitro, the MLV-H9N2 and MLV-H9N2-IL candidates demonstrated stability and virus titers comparable to the wild-type H9N2 strain. In chickens, the MLV-H9N2 and MLV-H9N2-IL candidates did not transmit via direct contact. Co-infection studies with wild-type virus confirmed that the altered HA and NA segments exhibited fitness disadvantages and did not reassort. Vaccinated chickens showed no clinical signs upon vaccination, all seroconverted, and the inclusion of ckIL18 in the MLV-H9N2-IL vaccine enhanced neutralizing antibody production. A significant decrease in viral loads post-challenge underscored the protective effect of the MLVs. The MLV-H9N2-IL vaccine, administered via drinking water, proved immunogenic in chickens in a dose-dependent manner, generating protective levels of neutralizing antibodies upon aggressive homologous virus challenge. In summary, this study lays the groundwork for safe MLVs against avian influenza suitable for mass vaccination efforts.

This study reports on the immunogenicity and biodistribution of H5 hemagglutinin (HA)-based self-amplifying (sa) mRNA vaccines in mice. Four sa-mRNA vaccines encoding either a secreted full-length HA, a secreted HA head domain, a secreted HA stalk domain, or a full-length membrane-anchored HA were investigated. All vaccines elicited an adaptive immune response. However, the full-length HA sa-RNA vaccines demonstrated superior performance compared to head and stalk domain vaccines. The antibody titers positively correlated with the vaccine dose. Cellular immune responses and antigen-specific IgA antibodies in the lungs were also observed. The comparison of the sa-mRNA vaccines encoding the secreted and membrane-anchored full-length HA revealed that anchoring of the HA to the membrane significantly enhanced the antibody and cellular responses. In addition to the injection site, the intramuscularly injected sa-mRNA-LNPs were also detected in the draining lymph nodes, spleen, and to a lesser extent, in the lung, kidney, liver, and heart.

Recent studies demonstrate that sociopolitical attitudes partially explain variance in (SARS-CoV-2) vaccine hesitancy and uptake. Other attitudes, such as those towards esoteric beliefs, complementary and alternative medicine (CAM), and religion, have also been proposed. However, pertinent studies provide limited direction for public health efforts, as the impact of such attitudes has been tested in isolation or on different outcomes. Moreover, related associations between SARS-CoV-2 immunization drivers as well as views towards other modes of immunization (e.g., routine pediatric immunization), remain unclear. Based on a sample of ~7400 survey participants (Germany), where esoteric belief systems and CAM (Waldorf, homeopathy) are rather prevalent, and controlling for other sociological factors, we found that (i) individuals with positive attitudes towards Waldorf education and homeopathy are significantly less likely to have received a (further) dose of SARS-CoV-2 vaccine compared to those with positive views of mainstream medicine; (ii) for the former, immunization decisions are primarily driven by external pressures, and for the latter overwhelmingly by voluntary considerations; (iii) attitudes influencing adult SARS-CoV-2 vaccine uptake similarly influence views towards routine pediatric immunization. Our findings provide significant evidence informing a more nuanced design of public health and communication campaigns, and pertinent policies.