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At least 19 recordsLinked to original sources
PubMed2015

New approaches to HIV vaccine development.

Development of a safe and effective vaccine for HIV is a major global priority. However, to date, efforts to design an HIV vaccine with methods used for development of other successful viral vaccines have not succeeded due to HIV diversity, HIV integration into the host genome, and ability of HIV to consistently evade anti-viral immune responses. Recent success in isolation of potent broadly neutralizing antibodies (bnAbs), in discovery of mechanisms of bnAb induction, and in discovery of atypical mechanisms of CD8T cell killing of HIV-infected cells, have opened new avenues for strategies for HIV vaccine design.

AIDS Vaccines↗
PubMed2026

Non-human primate LIBRA-Seq accelerates neutralizing antibody discovery in RM vaccinated against HIV-1.

Broadly neutralizing antibodies (bNAbs) exhibit protective efficacy against HIV-1 infection making them an ideal archetype for HIV-1 vaccine design. Presently, no vaccine candidate has induced antibody responses capable of meaningful protection against the swathe of circulating, difficult to neutralize tier 2 HIV-1 viruses. However, the development of stabilized, native-like envelope (Env) trimers such as BG505.SOSIP.664.T332N (BG505 SOSIP) has marked a significant advancement in vaccine design, due to their ability to elicit NAbs that neutralize tier 2 viruses in rhesus macaques (RM). NAb development following envelope trimer immunization in RM remains poorly understood, with hypothesized contributions from genetic variation at the IG loci, naive B cell repertoire, and differential gene expression in B cell lineages. To address these knowledge gaps, we have developed a set of BG505 SOSIP probes capable of recovering paired clonotype identity, antigen specificity, and gene expression of B cells in a high throughput fashion. These probes were constructed by conjugating biotinylated BG505 SOSIP to streptavidin covalently linked to both sc-RNA-Seq compatible DNA oligonucleotides and flow cytometry compatible fluorophores. Using these reagents, we isolated and sequenced BG505 SOSIP specific memory B cells from the PBMCs of an RM that developed high titers of neutralizing antibodies. To benchmark the accuracy of our technology, we compared our recovered heavy and light chain sequences to those identified from the same animal using conventional methodology and recovered 100% of previously identified NAbs. We then applied this technology to recover BG505 SOSIP specific memory B cells from five additional vaccinated RMs, cloned 34 antibodies for functional characterization, and identified ten antibodies with autologous neutralizing activity.

Animals↗
PubMed2025

Increased immunogen valency improves the maturation of vaccine-elicited HIV-1 VRC01-like antibodies.

Antibodies belonging to the VRC01-class display broad and potent neutralizing activities and have been isolated from several people living with HIV (PLWH). A member of that class, monoclonal antibody VRC01, was shown to reduce HIV-acquisition in two phase 2b efficacy trials. VRC01-class antibodies are therefore expected to be one component of an effective HIV-1 vaccine elicited response. In contrast to the VRC01-class antibodies that are highly mutated, their unmutated forms do not engage HIV-1 envelope (Env) and do not display neutralizing activities. Hence, specifically modified Env-derived proteins have been designed to engage the unmutated forms of VRC01-class antibodies, and to activate the corresponding naïve B cells. Selected heterologous Env must then be used as boost immunogens to guide the proper maturation of these elicited VRC01-class antibodies. Here we examined whether and how the valency of the prime and boost immunogens influences VRC01-class antibody-maturation. Our findings indicate that, indeed the valency of the immunogen affects the maturation of elicited antibody responses by preferentially selecting VRC01-like antibodies that have accumulated somatic mutations present in broadly neutralizing VRC01-class antibodies isolated from PLWH. As a result, antibodies isolated from animals immunized with the higher valency immunogens display broader Env cross-binding properties and improved neutralizing potentials than those isolated from animals immunized with the lower valency immunogens. Our results are relevant to current and upcoming phase 1 clinical trials that evaluate the ability of novel immunogens aiming to elicit cross-reactive VRC01-class antibody responses.

AIDS Vaccines↗
PubMed1978

Vaccination by the aerosol method.

After a review on vaccination by inhalation of aerosols the authors describe the group vaccination with the aid of an electroaerosol generator. 8 persons may be vaccinated simultaneously in a very short time. The vaccination by inhalation is without any hazards. The viability of the microorganisms in the aerosol is preserved. Interferon inhalation seems to reduce symptoms of intoxication in the first days after outset of influenza or acute airway infection. The efficiency of vaccination through aerosol inhalations against bacterial infections demands further researchs.

Aerosols↗
PubMed1978

An electroaerosol device for group vaccination against influenza.

With the aid of an electroaerosol device a group of persons were vaccinated by inhalation of influenza vaccine. In a first trial 76 persons with a low antibody level (1 : 20 and less) were vaccinated against A2/Victoria/1/72 and B/USSR/69: Antibodies were reexamined 30 days later, Interferon at the 3rd and 10th day. This kind of vaccination caused an antibody increase statistically significant. In the course of an influenza epidemic 2,300 persons vaccinated by inhalation were compared with 2,195 not vaccinated. Among the persons vaccinated there were 13.7 +/- 0.7% diseases, among the non vaccinated persons 26.3 +/- 0.9%.

Aerosols↗
PubMed1978

Bordetella pertussis serotypes in Canada.

A study was done to determine the major antigenic factors of Bordetella pertussis strains isolated throughout Canada and whether these isolates have the same antigenic structure as the bacilli in the currently used vaccines. Testing for the major pertussis antigens, factors 1, 2 and 3, was conducted with 440 freshly isolated strains of B. pertussis received from seven canadian provinces between August 1976 and February 1978 and six batches of pertussis vaccine or immunizing agents containing pertussis vaccine. With the aid of specific antisera prepared in rabbits, the antigenic factors were detected by a slide agglutination technique. Almost all (98.9%) of the pertussis strains examined were serotype 1,3. All six batches of pertussis vaccine or immunizing agents containing pertussis vaccine proved to be rich in each of the three main pertussis agglutinogens.

Antigens, Bacterial↗
PubMedDate not supplied

[Detection of tubercular infection after BCG vaccination].

The author has followed several groups of children over a period of many years and evidenced the general decrease of the level of tuberculin reactivity. The implications are discussed, of the B.C.G. vaccination on the tuberculous allergy and the possibility to differentiate post-vaccinal allergy with the aid of skin testing, using 2 and 10 PPD units. The importance is stressed, of the vaccinal scar as an indication of a good immune reactivity, and thus of protection against contamination with virulent tuberculous baccili. The time is foreseen, when systematic vaccination with B.C.G. will reduce to such a significant degree the number of cases of tuberculosis in children that differential diagnosis on the basis of tuberculin allergy will not be necessary.

Adolescent↗
PubMed1975

[Enteral immunization with attenuated representatives of the family Enterobacteriaceae. Report 3. Comparison of the immunogenicity of the Sm-d-mutants of E. coli and the killed vaccine].

The authors present the results of a comparative study of the immunogenicity of the living (Sm-d) and killed E. coli vaccine which, in determination by such methods as the Vidal test, passive hemagglutination test, bactericidal activity, establishment of passive and active defence, proved to be the same in both vaccines. However, with the aid of Rauss and Ketyi's method, modified by the authors (determination of nonsuceptibility in enteral infection of the animals with intestine sterilized with streptomycin) it was possible to reveal the capacity of the living vaccine to depress the growth and the activity (reproducible and statistically controlled) of E. coli administered into the organism of the immunized animal for the purpose of infection. They were discharged with the feces for a definite period in 90% of control animals and mice immunized with the killed vaccine; this occured in less than 10% of the animals immunized with the living vaccine.

Animals↗
PubMed1979

Composition and evaluation of the efficacy of Staphylococcus aureus vaccine.

An alum-precipitated Staphylococcus aureus vaccine, composed of a formalin-inactivated whole culture of a strain which produces Smith surface antigen and combined with the whole culture of a highly toxigenic strain, was found to afford a good immunity to staphylococcal skin infection in rabbits. Three injections of the vaccine provided immunity which lasted for at least 6 months against a primarily pyogenic strain of S. aureus and for at least 3 months against a toxigenic strain. From experiments using vaccines prepared from cells or toxoid only, it was deduced that, although there is a measure of strain specific immunity, a good heterologous immunity can be established with a combined product provided that it contains adequate quantities of toxoid. The use of such a vaccine as a potential aid in the control of bovine staphylococcal mastitis is discussed.

Adjuvants, Immunologic↗
PubMed2026

Religious beliefs and practices, political orientation, and distrust in healthcare predict attitudes toward mRNA vaccines in the United States.

Religion has contributed to societal divides regarding COVID-19 mRNA vaccines. In this study, we conducted a secondary analysis of a survey of U.S. adults (N=4939) focused on how religious affiliations, beliefs, and practices impact attitudes toward genetic and genomic activities, one of which was mRNA vaccines. The dataset included large samples of participants from six religious groups in the U.S. (Black Protestant, Catholic, Evangelical Protestant, Jewish, Mainline Protestant, and Muslim), as well as individuals who were atheist, agnostic, or spiritual. ANCOVA results indicated that Evangelical Protestant participants showed significantly less support for mRNA vaccines than other groups, while atheist participants were the most supportive. Muslim participants had the highest concerns, whereas atheist participants had the lowest. Regression analyses indicated the strongest predictors of support for mRNA vaccines were more spiritual community support for community health, followed by higher acceptance of evolution, more liberal political orientation, less distrust toward the healthcare system, higher frequency of attending religious activities, higher income, lower fundamentalist religious beliefs, and more spiritual community support for liberal reproductive and end of life views. The strongest predictors of concerns about mRNA vaccines were more distrust toward the healthcare system and more conservative political orientation, followed by less spiritual community support for community health, stronger beliefs about God in the body, more fundamentalist religious beliefs, and lower knowledge of genetics. The large sample size, and examination of a broad array of religious variables alongside distrust and political orientation offer new insights. These findings add to the literature on the culture wars surrounding mRNA vaccines, and can perhaps aid in future efforts to build trust and relationships between public health and religious communities.

genomic medicine↗
PubMed2026

Religious beliefs and practices, political orientation, and distrust in healthcare predict attitudes toward mRNA vaccines in the United States.

Religion has contributed to societal divides regarding COVID-19 mRNA vaccines. In this study, we conducted a secondary analysis of a survey of U.S. adults (N = 4939) focused on how religious affiliations, beliefs, and practices impact attitudes toward genetic and genomic activities, one of which was mRNA vaccines. The dataset included large samples of participants from six religious groups in the U.S. (Black Protestant, Catholic, Evangelical Protestant, Jewish, Mainline Protestant, and Muslim), as well as individuals who were atheist, agnostic, or spiritual. ANCOVA results indicated that Evangelical Protestant participants showed significantly less support for mRNA vaccines than other groups, while atheist participants were the most supportive. Muslim participants had the highest concerns, whereas atheist participants had the lowest. Regression analyses indicated the strongest predictors of support for mRNA vaccines were more spiritual community support for community health, followed by higher acceptance of evolution, more liberal political orientation, less distrust toward the healthcare system, higher frequency of attending religious activities, higher income, lower fundamentalist religious beliefs, and more spiritual community support for liberal reproductive and end of life views. The strongest predictors of concerns about mRNA vaccines were more distrust toward the healthcare system and more conservative political orientation, followed by less spiritual community support for community health, stronger beliefs about God in the body, more fundamentalist religious beliefs, and lower knowledge of genetics. The large sample size and examination of a broad array of religious variables alongside distrust and political orientation offer new insights. These findings add to the literature on the culture wars surrounding mRNA vaccines, and can perhaps aid in future efforts to build trust and relationships between public health and religious communities.

Journal Article↗
PubMed2024

An isoform-resolution transcriptomic atlas of colorectal cancer from long-read single-cell sequencing.

Colorectal cancer (CRC) ranks as the second leading cause of cancer deaths globally. In recent years, short-read single-cell RNA sequencing (scRNA-seq) has been instrumental in deciphering tumor heterogeneities. However, these studies only enable gene-level quantification but neglect alterations in transcript structures arising from alternative end processing or splicing. In this study, we integrated short- and long-read scRNA-seq of CRC samples to build an isoform-resolution CRC transcriptomic atlas. We identified 394 dysregulated transcript structures in tumor epithelial cells, including 299 resulting from various combinations of splicing events. Second, we characterized genes and isoforms associated with epithelial lineages and subpopulations exhibiting distinct prognoses. Among 31,935 isoforms with novel junctions, 330 were supported by The Cancer Genome Atlas RNA-seq and mass spectrometry data. Finally, we built an algorithm that integrated novel peptides derived from open reading frames of recurrent tumor-specific transcripts with mass spectrometry data and identified recurring neoepitopes that may aid the development of cancer vaccines.

Colorectal Neoplasms↗
PubMed1975

The control of bluetongue in an enzootic situation.

On account of the wide host range of bluetongue virus and its biological transmission by insects, control of the disease in an enzootic situation is based primarily on the active immunisation of susceptible animals as well as on the prevention of contact between the insect vectors and the susceptible hosts. In spite of their unquestionable value, the egg attenuated vaccines which are currently employed for prophylactic immunisation, have certain shortcomings. The existence of 16 known serotypes of bluetongue virus makes it difficult to achieve a very wide spectrum of immunity in sheep vaccinated once or twice only. The problems which are experienced with the immunisation of lambs born in spring are indicated. The present vaccine can also present problems when used in breeding animals. Furthermore, the costs involved in the annual vaccination of large numbers of animals are considerable. The need for a vaccine for cattle is indicated. Work is also being conducted at present on the development of an inactivated vaccine for use in sheep. The use of novel virological techniques may aid in the future development of absolutely safe and highly efficient vaccines against bluetongue.

Animals↗
PubMed1978

Recent developments in vaccination against bovine brucellosis.

Recent research in vaccination against bovine brucellosis has been directed towards reducing the serological response to vaccination and to developing serological tests better able to distinguish vaccinal titres from those resulting from field infection. In the case of strain 19 vaccination, developments such as reducing the dose of vaccine and improving serological tests have so reduced the serological response as to allow adult vaccination to be carried out in combination with eradiction by test and slaughter. B. abortus 45/20 vaccine is being increasingly used as a combined diagnostic aid and protective agent. Progress has been made in identifying antibodies produced in response to this vaccine.

Agglutination Tests↗
PubMed2026

Whole-genome prediction of bacterial pathogenic capacity on novel bacteria using protein language models with PathogenFinder2.

MOTIVATION: Infectious diseases continue to be a leading cause of mortality and pose a significant global health threat. Thus, the development of tools for surveillance and early detection of emerging pathogens is needed. RESULTS: We introduce PathogenFinder2, a novel, alignment-free, taxonomy-agnostic model for predicting bacterial pathogenic capacity in humans using protein language models. It outperforms previous methods, particularly for novel taxa, and provides interpretable outputs by highlighting proteins most relevant to pathogenic potential. These insights aid the identification of virulence factors, vaccine targets, and infection-related metabolic pathways. Furthermore, we introduce the Bacterial Pathogenic Capacity Landscape, which reveals patterns linked to host condition, infection site, microbial antagonism, and environmental origin. AVAILABILITY: The model is freely available online at https://genepi.dk/pathogenfinder2, or as a standalone program (https://github.com/genomicepidemiology/PathogenFinder2).

Genome, Bacterial↗
PubMed1976

[Localization of specific antigen in the organs of animals inoculated with live measles vaccine].

There was a short-lived localization of the antigen of the attenuated measles virus in the neurons and the vessels of the brain in the newborn mice and hamsters inoculated subcutaneously with live measles vaccine. In adult animals the virus specific antigen was revealed in the lymphoid system only. As to the brain tissue of the inoculated animals, the symptoms of serous meningitis and vascular disturbances were observed for a brief period of time. The vaccinal measles virus was not isolated from the brain tissue with the aid of the biotest on tissue culture.

Animals↗
PubMedDate not supplied

Control of viability, thermostability and residual virulene of BCG vaccines. Multiple comparison of laboratory data to select products for immunostimulation in the treatment of cancer.

UNLABELLED: The aid of the work was to apply the multiple comparison method to select BCG products for immunostimulation. In the IABS-BCG Collaborative Study 1973 program coded BCG products (code) and reference preparation were investigated with 3 laboratory tests to compare differences concerning: (1) viability = viable units E6/ml (VU) of vaccines stored at 4C, (2) 37C thermostability (TS) slope = daily VU decrease of vaccines stored at 37C/0, 7, 14, 21, 28 days, (3) relative persistence capacity (RPC),--residual virulence--of the BCG strains in the mice spleen; regression followed up to 360 days. Culturable particles and recoverable VU were determined on BOAA medium. Means and regression coefficients of VU, TS and RPC were ranked after analysis of variance and evaluated by multiple-comparison-Gabriel method. Figures summarize the results. As to VU the products form 3 subsets; as to TS the products are in two subsets (ie potency of several products could be included in the same subset). Thus, the ranks of VU and TS are not the same. Also there are differences among overall rank of RPC (coefficient concordance of ranks of 2 VU doses, log and sqrt transformation of exp. data) and the VU as well as the TS. CONCLUSION: parallel VU, TS and RPC investigations and multiple comparison method could ensure the validity and reliability of the estimations in the quality control of products for immunostimulation and could explain the correlations and contradictions between the laboratory data and the results of the clinical trial in neoplasia.

Animals↗