Vaccine Composition Research Articles

Informing the Need for a SARS-CoV-2 Booster Based on the Immune Responses Among Young Healthy Adults to Variants Circulating in Late 2023.

COVID-19 remains a global public health challenge due to new immune-evasive SARS-CoV-2 variants and heterogeneous immunity. In this cross-sectional study, we evaluated the adaptive immune responses in US active duty personnel who completed a COVID-19 primary vaccine series and had heterogenous SARS-CoV-2 vaccination and infection histories to 3 previously dominant variants (ancestral, Delta, BA.5) and 3 circulating variants (XBB.1.5, EG.5, and BA.2.86) in late 2023. Analyses were based on the most recent exposure in terms of timing (within or beyond 12 months) and type (vaccine or infection). Significant reduction was observed in binding antibodies, neutralization antibodies, memory B cells, and CD8+ T cells against circulating variants when compared with previous variants. The reduction in antibody response was more pronounced in those whose most recent exposure was >12 months from enrollment. In contrast, the CD4+ T-cell response was largely consistent across all tested variants. The type of most recent exposure was not a significant factor in determining the magnitude of current immune responses. Administration of the XBB.1.5-based booster is likely to enhance cross-reactive humoral responses against SARS-CoV-2 circulating lineages. Ongoing surveillance of immune responses to emerging variants is needed for informing vaccine composition and timing.

February 2024 ACIP Meeting Update: Meningococcal, RSV, COVID-19, and Other Vaccines.

The Advisory Committee on Immunization Practices, a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention, normally meets 3 times per year to develop US vaccine recommendations. The Advisory Committee on Immunization Practices met February 28 to 29, 2024, to discuss coronavirus disease 2019 vaccines, chikungunya vaccines, diphtheria-tetanus vaccine, influenza vaccines, polio vaccines, respiratory syncytial virus vaccines, meningococcal vaccines, pneumococcal vaccines, and Vaxelis (Diphtheria, Tetanus, Pertussis, Inactivated Poliovirus, Haemophilus influenzae b Conjugate, and Hepatitis B Vaccine). This update summarizes the proceedings of these meetings, with an emphasis on topics that are most relevant to the pediatric population. Major updates for pediatric clinicians include information about changes on influenza vaccine composition, meningococcal vaccination considerations, updated guidance for children with a contraindication to pertussis-containing vaccines, and recommendations of the world's first chikungunya vaccine for certain populations.

NeoAgDT: optimization of personal neoantigen vaccine composition by digital twin simulation of a cancer cell population.

Neoantigen vaccines make use of tumor-specific mutations to enable the patient's immune system to recognize and eliminate cancer. Selecting vaccine elements, however, is a complex task which needs to take into account not only the underlying antigen presentation pathway but also tumor heterogeneity. Here, we present NeoAgDT, a two-step approach consisting of: (i) simulating individual cancer cells to create a digital twin of the patient's tumor cell population and (ii) optimizing the vaccine composition by integer linear programming based on this digital twin. NeoAgDT shows improved selection of experimentally validated neoantigens over ranking-based approaches in a study of seven patients. The NeoAgDT code is published on Github: https://github.com/nec-research/neoagdt.

Major Role of S-Glycoprotein in Providing Immunogenicity and Protective Immunity in mRNA Lipid Nanoparticle Vaccines Based on SARS-CoV-2 Structural Proteins.

SARS-CoV-2 variants have evolved over time in recent years, demonstrating immune evasion of vaccine-induced neutralizing antibodies directed against the original S protein. Updated S-targeted vaccines provide a high level of protection against circulating variants of SARS-CoV-2, but this protection declines over time due to ongoing virus evolution. To achieve a broader protection, novel vaccine candidates involving additional antigens with low mutation rates are currently needed. Based on our recently studied mRNA lipid nanoparticle (mRNA-LNP) platform, we have generated mRNA-LNP encoding SARS-CoV-2 structural proteins M, N, S from different virus variants and studied their immunogenicity separately or in combination in vivo. As a result, all mRNA-LNP vaccine compositions encoding the S and N proteins induced excellent titers of RBD- and N-specific binding antibodies. The T cell responses were mainly specific CD4+ T cell lymphocytes producing IL-2 and TNF-alpha. mRNA-LNP encoding the M protein did not show a high immunogenicity. High neutralizing activity was detected in the sera of mice vaccinated with mRNA-LNP encoding S protein (alone or in combinations) against closely related strains, but was undetectable or significantly lower against an evolutionarily distant variant. Our data showed that the addition of mRNAs encoding S and M antigens to mRNA-N in the vaccine composition enhanced the immunogenicity of mRNA-N and induced a more robust immune response to the N protein. Based on our results, we suggested that the S protein plays a key role in enhancing the immune response to the N protein when they are both encoded in the mRNA-LNP vaccine.

Генотипическая характеристика штаммов Bordetella pertussis — кандидатов для получения коклюшного компонента вакцинных препаратов (сообщение I)

Vaccination is an effective means of preventing pertussis infection. The purpose of this work was to improve vaccines available in the Russian Federation in general and actualize vaccine strains used for the production thereof in particular. We studied B. pertussis strains isolated in Moscow, Voronezh, Novosibirsk, Ulyanovsk and Chelyabinsk regions, and eight production strains part of the adsorbed diphtheria-pertussis-tetanus (DPT) vaccine. Multilocus antigenic sequence typing (MAST) and whole genome multilocus sequence typing (wgMLST) were used for genotyping. We studied cultural morphological, enzymatic, serological, and genotypic properties of the candidate B. pertussis strains, and compared their genotypic properties to those of B. pertussis vaccine strains from the current composition of the DPT vaccine. Candidate strains belong to four genotypes: ptxА1/ptxВ2/ptxС2/ptxР3/fim2-2/fim3-2/prn2, ptxА1/ptxВ2/ptxС2/ptxР3/fim2-2/fim3-2/prn9, ptxА1/ptxВ2/ptxС2/ptxР3/fim2-1/fim3-1/prn1 and ptxА1/ptxВ2/ptxС2/ptxР3/fim2-2/fim3-1/prn2. Current vaccine strains were from other six genotypes: ptxА2/ptxВ1/ptxС1/ptxР1/fim2-1/fim3-1/prn1, ptxА2/ptxВ2/ptxС1/ptxР2/fim2-1/fim3-1/prn1, ptxА4/ptxВ1/ptxС1/ptxР2/fim2-1/fim3-1/prn1, ptxА2/ptxВ2/ptxС1/ptxР1/fim2-1/fim3-1/prn1, ptxА4/ptxВ2/ptxС1/ptxР2/fim2-1/fim3-1/prn1 and ptxА1/ptxВ2/ptxС1/ptxР1/fim2-1/fim3-1/prn1. With the help of wgMLST, we established affiliation of all candidate strains of B. pertussis to ST2.

Abstract 4106: A novel synthetic long peptide vaccine composition targeting multiple PD-L1 T-cell epitopes exhibits anti-tumor efficacy in a syngeneic mouse colorectal cancer model

Abstract Background Cancer immunotherapy targeting immune checkpoints has shown promising clinical anti-tumor efficacy over the past decades. Monoclonal antibodies against PD-1 or PD-L1 have demonstrated clinical efficacy in a wide spectrum of cancer types. Despite the clinical success of therapies using immune checkpoint inhibitors (ICI), only a subset of patients shows long-lasting tumor remission, while resistance and toxicities to these agents remain to be addressed. This supports the need to explore alternative immunotherapeutic approaches or additional therapies for synergistic combinations to augment the anti-tumor efficacy for cancer patients receiving ICI therapies. Methods As an active immunotherapy approach, we developed a blend of four novel synthetic peptide vaccines each containing one PD-L1 T-cell epitope with individual covalent conjugation of the carrier protein, keyhole limpet haemocyanin (KLH), which is to break immune tolerance towards self-molecules. The four PD-L1 epitopes range from 30 to 40 amino acids in length, which target different domains of mouse PD-L1 protein. The PD-L1 peptides were synthesized using the technique of solid-phase peptide synthesis and purified by high performance liquid chromatography. All naked peptides were conjugated to KLH protein by thiol-maleimide reaction, followed by dialysis for purification. The peptide vaccines were formulated with a Toll-like receptor 9 agonist CpG ODN 1826 and aluminum hydroxide gel for animal immunization. Results These synthetic long PD-L1 peptide vaccines are highly immunogenic in a syngeneic BALB/c mouse model for a cell-mediated immune response when admixed and formulated with adjuvants. The vaccine composition is well tolerated by the mice with no evidence of toxicity and autoimmunity. In vivo administration of the vaccine formulation can elicit a positive PD-L1-specific T cell response in splenocytes with an IFN-γ ELISPOT assay. Moreover, in vivo vaccination of these PD-L1 peptide vaccines in a CT26 syngeneic mouse preventive colorectal cancer model exhibits a potent anti-tumor activity, with a 54% tumor growth inhibition (p<0.001) in tumor volume compared to that of the adjuvant-control group at the end of the study. Conclusions Taken together, our data demonstrate a proof-of-concept that T cell-based PD-L1 peptide vaccines are a promising therapeutic strategy for inducing anti-tumor immunity to combat cancers. Citation Format: Kenneth Nansheng Lin, Melvin Toh. A novel synthetic long peptide vaccine composition targeting multiple PD-L1 T-cell epitopes exhibits anti-tumor efficacy in a syngeneic mouse colorectal cancer model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4106.

Testing of diagnostic test-systems for detection of antibodies to foot-and-mouth disease virus structural proteins with enzyme-linked immunosorbent assay for their serotype specificity

A total of 138 serum samples from pigs and cattle vaccinated against foot-and-mouth disease virus (FMDV) of one or two serotypes or infected with FMDV were used for testing of 24 enzyme-linked immunosorbent assay (ELISA) diagnostic tests-systems for detection of antibodies against FMDV structural proteins produced by 6 manufacturers (Federal Centre for Animal Health, Prionics, IZSLER, Innovative Diagnostics, BIONOTE and MEDIAN Diagnostics) for their serotype-specificity. All used test-systems detected apparent serotype-specific activity (homologous reaction) as well as cross-reacting virus-specific antibodies that was accounted for some reasons related to conservative epitopes in amino acid sequence of FMDV virion capsid VP1–VP3 polypeptides, accessibility of internal conservative epitopes of VP4 polypeptide for the animal’s immune system during virus replication or vaccine antigen (virus) destruction in the animal’s body in the process of immunity development, as well as the pilot anti-FMD vaccine composition, etc. Nevertheless, the analysis of a large data set (about 3,500 tests) showed that the homologous serotype-specific reaction in general was significantly higher and predominant, the proportion of virus-specific non-protective antibodies, including cross-reacting ones, was not significant and did not distort the results of ELISA tests of anti-FMD vaccine for its immunogenicity. Inconclusive test results require confirmation with other serological tests. Complex tests for FMDV using different diagnostic methods such as ELISA with standard and reference test-systems and/or virus neutralization test in cell culture are to be considered as the best option.

Properties of influenza viruses that caused epidemic increases in morbidity in Russia and countries of the world during 2022–2023. The effectiveness of vaccine prophylaxis

The purpose of this work was to determine the characteristics of the circulation of various viral respiratory pathogens during the epidemic season 2022–2023 against the background of the ongoing evolutionary variability of SARS-CoV-2.
 Materials and methods. The article uses methods used in «traditional» and «hospital» epidemiological surveillance of acute respiratory viral infections.
 Results and discussion. The period from October 2022 to September 2023 was characterized by early and high activity of influenza A(H1N1)pdm09 virus, which was replaced by influenza B virus. The antigenic and genetic properties of strains were closely related to influenza vaccines viruses recommended by WHO experts for the current season. The effectiveness of influenza vaccines was confirmed (75.0%). All of the studied influenza A(H1N1)pdm09, A(H3N2) and B epidemic strais retained sensitivity to drugs with antineuraminidase activity. The structure and share of other ARVI pathogens have changed somewhat compared to the previous season: There was a tendency to increase the activity of HAdV and HMPV; almost equivalent activity of HRsV, HRV, HCoV and HBoV; and a decrease in HPIV activity. At the same time, the frequency of other ARVI pathogens did not reach the indicators of the pre-pandemic COVID-19 period. The rationale for updating the composition of influenza vaccines for the countries of the Northern Hemisphere in the 2023–2024 season is given.

New Approaches to the Prevention of Visceral Leishmaniasis: A Review of Recent Patents of Potential Candidates for a Chimeric Protein Vaccine.

The development of prophylactic vaccines is important in preventing and controlling diseases such as visceral leishmaniasis (VL), in addition to being an economic measure for public health. Despite the efforts to develop a vaccine against human VL caused by Leishmania infantum, none is available, and the focus has shifted to developing vaccines against canine visceral leishmaniasis (CVL). Currently, commercially available vaccines are targeted at CVL but are not effective. Different strategies have been applied in developing and improving vaccines, such as using chimeric proteins to expand vaccine coverage. The search for patents can be a way of tracking vaccines that have the potential to be marketed. In this context, the present work presents a summary of immunological aspects relevant to VL vaccine development with a focus on the composition of chimeric protein vaccines for CVL deposited in patent banks as an important approach for biotechnological development. The resulting data could facilitate the screening and selection of antigens to compose vaccine candidates with high performance against VL.

O-Antigen decorations in Salmonella enterica play a key role in eliciting functional immune responses against heterologous serovars in animal models.

Different serovars of Salmonella enterica cause systemic diseases in humans including enteric fever, caused by S. Typhi and S. Paratyphi A, and invasive nontyphoidal salmonellosis (iNTS), caused mainly by S. Typhimurium and S. Enteritidis. No vaccines are yet available against paratyphoid fever and iNTS but different strategies, based on the immunodominant O-Antigen component of the lipopolysaccharide, are currently being tested. The O-Antigens of S. enterica serovars share structural features including the backbone comprising mannose, rhamnose and galactose as well as further modifications such as O-acetylation and glucosylation. The importance of these O-Antigen decorations for the induced immunogenicity and cross-reactivity has been poorly characterized. These immunological aspects were investigated in this study using Generalized Modules for Membrane Antigens (GMMA) as delivery systems for the different O-Antigen variants. This platform allowed the rapid generation and in vivo testing of defined and controlled polysaccharide structures through genetic manipulation of the O-Antigen biosynthetic genes. Results from mice and rabbit immunization experiments highlighted the important role played by secondary O-Antigen decorations in the induced immunogenicity. Moreover, molecular modeling of O-Antigen conformations corroborated the likelihood of cross-protection between S. enterica serovars. Such results, if confirmed in humans, could have a great impact on the design of a simplified vaccine composition able to maximize functional immune responses against clinically relevant Salmonella enterica serovars.

Unlocking the Power of Influenza Vaccines for Pediatric Population: A Narrative Review.

The flu, often known as influenza, is a dangerous public health hazard for the pediatric population. Immunization is essential for decreasing the burden of the disease and avoiding complications related to influenza. However, the immunogenicity, efficacy, and safety of different influenza vaccines in children warrant careful evaluation. The purpose of this narrative review is to give a summary of the existing literature on the immunogenicity, efficacy, and safety of several vaccinations against influenza viruses in children. The review incorporates evidence from a range of studies focusing on the outcomes of interest. Immunogenicity studies have shown that influenza vaccines induce a robust immune response in children, primarily through neutralizing antibodies' formation. However, variations in vaccine composition influence the duration and magnitude of immune responses. Safety is a crucial consideration in pediatric vaccination. In children, influenza vaccinations have generally shown a high safety profile, with mild and temporary side effects being the most common. Vaccinations against influenza have shown a modest level of efficacy in avoiding hospitalizations linked to influenza, laboratory-confirmed influenza infections, and serious consequences in children. Live attenuated vaccines have shown higher effectiveness against matched strains compared to inactivated vaccines. In conclusion, this narrative review highlights that receiving influenza vaccination in children aged six to 47 months is very important. While different vaccines exhibit varying immunogenicity, safety profiles, and effectiveness, they all contribute to reducing the burden of influenza among children. Future research should focus on optimizing vaccine strategies, improving vaccine coverage, and evaluating long-term protection.

First Reported Circulation of Equine Influenza H3N8 Florida Clade 1 Virus in Horses in Italy.

Equine influenza (EI) is a highly contagious viral disease of equids characterized by pyrexia and respiratory signs. Like other influenza A viruses, antigenic drift or shift could lead to a vaccine-induced immunity breakdown if vaccine strains are not updated. The aim of this study was to genetically characterize EIV strains circulating in Italy, detected in PCR-positive samples collected from suspected cases, especially in the absence of formal active surveillance. Between February and April 2019, blood samples and nasal swabs collected from each of the 20 symptomatic horses from North and Central Italy were submitted to the National Reference Centre for Equine Diseases in Italy to confirm preliminary analysis performed by other laboratories. None of the sera analysed using haemagglutination inhibition and single radial haemolysis presented a predominant serological reactivity pattern for any antigen employed. All nasal swabs were positive with IAV RRT-PCR. Only one strain, isolated in an embryonated chicken egg from a sample collected from a horse of a stable located in Brescia, Lombardy, was identified as H3N8 Florida lineage clade 1 (FC1). In the constructed phylogenetic trees, this strain is located within the FC1, together with the virus isolated in France in 2018 (MK501761). This study reports the first detection of H3N8 FC1 in Italy, highlighting the importance of monitoring circulating EIV strains to verify the vaccine composition appropriateness for maximum efficacy.

Development of Cross-Reactive Live Attenuated Influenza Vaccine Candidates against Both Lineages of Influenza B Virus.

Influenza viruses continue to cause a significant social and economic burden globally. Vaccination is recognized as the most effective measure to control influenza. Live attenuated influenza vaccines (LAIVs) are an effective means of preventing influenza, especially among children. A reverse genetics (RG) system is required to rapidly update the antigenic composition of vaccines, as well as to design LAIVs with a broader spectrum of protection. Such a system has been developed for the Russian LAIVs only for type A strains, but not for influenza B viruses (IBV). All genes of the B/USSR/60/69 master donor virus (B60) were cloned into RG plasmids, and the engineered B60, as well as a panel of IBV LAIV reassortants were rescued from plasmid DNAs encoding all viral genes. The engineered viruses were evaluated in vitro and in a mouse model. The B60 RG system was successfully developed, which made it possible to rescue LAIV reassortants with the desired antigenic composition, including hybrid strains with hemagglutinin and neuraminidase genes belonging to the viruses from different IBV lineages. The LAIV candidate carrying the HA of the B/Victoria-lineage virus and NA from the B/Yamagata-lineage virus demonstrated optimal characteristics in terms of safety, immunogenicity and cross-protection, prompting its further assessment as a broadly protective component of trivalent LAIV. The new RG system for B60 MDV allowed the rapid generation of type B LAIV reassortants with desired genome compositions. The generation of hybrid LAIV reassortants with HA and NA genes belonging to the opposite IBV lineages is a promising approach for the development of IBV vaccines with broad cross-protection.

Epidemiology of influenza in Nigeria: A secondary analysis of the sentinel surveillance data in Nigeria from 2010 – 2020

BackgroundInfluenza is a leading cause of morbidity and mortality globally. Little is known of the true burden and epidemiology of influenza in Africa. Nigeria has a sentinel surveillance system for influenza virus (IFV). This study seeks to describe the epidemiological characteristics of influenza cases in Nigeria through secondary data analysis of the sentinel surveillance data from 2010 to 2020. MethodologyA retrospective secondary data analysis of data collected from patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) in the four Nigeria Influenza Sentinel Surveillance sites from January 2010 to December 2020. Data was cleaned and analyzed using Microsoft Excel and Epi info 7.2 for frequencies and proportions. The results of the analysis were summarized in tables and charts. ResultsA total of 13,828 suspected cases of influenza were recorded at the sentinel sites during the study period. About 10.3% (1421/13,828) of these tested positive for IFV of which 1243 (87.5%) were ILI patients, 175 (12.3%) SARI patients, and 3 (0.2%) novel H1N1 patients. Males accounted for 54.2% (770/1421) of the confirmed cases. The median age of confirmed cases was 3 years (range: <1month–97 years). Children 0–4 years accounted for 69.3% (985/1421) of all cases. The predominant subtypes were B lineage not determined (32.3%), A/H1N1 pdm09 (28.8%) and A/H3 (23.0%). There were periods of sustained transmission in most years with 2011 having the highest number of cases. Overall, there were more cases around January to March and August to November. Heart disease and chronic shortness of breath were the most common co-morbidities identified among confirmed cases. ConclusionInfluenza remains a significant cause of respiratory illness, especially among children aged less than 4 years. Influenza cases occur all year round with irregular seasonality in Nigeria. Children less than 4 years and those with co-morbidities should be prioritized for vaccination. Vaccine composition in the country should take cognizance of the prevailing strains which are type B (lineage not determined), A/H1N1 pdm09 and A/H3.

Перспективы применения иммуно-ПЦР в диагностике SARS-CоV-2

One of the main biological characteristics of SARS-CoV-2 is its remarkable ability to adapt to new environmental conditions. Accelerated evolution of the COVID-19 pathogen complicates anti-epidemic measures, including the need to update the antigenic composition of vaccines and maintain current vaccination measures, complicates the prognosis of the infection course, and reduces the efficacy of drugs based on monoclonal antibodies and specific antiviral inhibitors. Under these conditions, the search for new approaches to monitoring clinically and epidemiologically significant variants of the virus that escape the factors of humoral immunity, as well as to the accelerated development of relevant immunobiological preparations, becomes important. This in turn requires the use of approaches to assess the serological properties of new variants, such as neutralization reactions using live infectious virus or immunochemical methods with limited antigen detection. Immuno-PCR (iPCR) is a method which is lacked majority of virus neutralization reaction and immunochemical methods (ELISA and LFT) disadvantages. The iPCR method has many modifications aimed at increasing specificity while reducing background amplification, simplifying staging, and multiplexing. Taking into account the high sensitivity of iPCR, it is possible not only to measure the exact amount of antigen, but also to use the diagnostics in the minimum quantities available, for example, in clinical samples. This fact makes iPCR method high-promising in personalized medicine field. Key words: SARS-CoV-2, coronavirus evolution, immuno-PCR, humoral immunity

Screening for lipid nanoparticles that modulate the immune activity of helper T cells towards enhanced antitumour activity.

Lipid nanoparticles (LNPs) can be designed to potentiate cancer immunotherapy by promoting their uptake by antigen-presenting cells, stimulating the maturation of these cells and modulating the activity of adjuvants. Here we report an LNP-screening method for the optimization of the type of helper lipid and of lipid-component ratios to enhance the delivery of tumour-antigen-encoding mRNA to dendritic cells and their immune-activation profile towards enhanced antitumour activity. The method involves screening for LNPs that enhance the maturation of bone-marrow-derived dendritic cells and antigen presentation in vitro, followed by assessing immune activation and tumour-growth suppression in a mouse model of melanoma after subcutaneous or intramuscular delivery of the LNPs. We found that the most potent antitumour activity, especially when combined with immune checkpoint inhibitors, resulted from a coordinated attack by T cells and NK cells, triggered by LNPs that elicited strong immune activity in both type-1 and type-2 T helper cells. Our findings highlight the importance of optimizing the LNP composition of mRNA-based cancer vaccines to tailor antigen-specific immune-activation profiles.

The history of vaccine and vaccination against influenza in Poland

The influenza virus is an important cause of morbidity, complications and mortality worldwide. Anyone can be infected, regardless of latitude or age. The paper describes the history of obtaining a modern influenza vaccine that does not deviate from current World Health Organization standards in Poland. Dozens of studies assessing the post-vaccination humoral response for different types of influenza vaccine, measuring levels of anti-haemagglutinin and anti-neuraminidase antibodies (although not in all of the studies) have been presented. The research was conducted mainly in high-risk populations, regardless of the age of vaccine recipients. What is noteworthy, the paper presents specific examples that may help promote prevention and encourage healthcare personnel to protect not only patients, but also their relatives. Prophylaxis in the form of vaccination is the cheapest and most effective form of preventing both dangerous complications and mortality. Infection caused by the influenza virus should be viewed not only in the context of exacerbation of a pre-existing disease or causing a new disease, but also in terms of measurable public costs. There are many types of imported influenza vaccines available on the Polish pharmaceutical market, from the inactivated intramuscular split or subunit vaccine to the intranasal live vaccine obtained from strains adapted to lower replication temperatures. Currently, quadrivalent influenza vaccines, i.e. containing two influenza A virus subtypes (A/H1N1/pdm09, A/H3N2) and two influenza B virus lineages (Victoria and Yamagata), are used. Depending on the type of vaccine, immunisation is recommended from the age of 6 months, whereas the upper age limit is not specified. The composition of vaccines is updated every epidemic season.

Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting.

The continuing emergence of SARS-CoV-2 variants highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by vaccination based on the ancestral (hereafter referred to as WT) strain would compromise the antibody response to Omicron-based boosters1-5. Vaccination strategies to counter immune imprinting are critically needed. Here we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. In mice, the efficacy of single Omicron boosting is heavily limited when using variants that are antigenically distinct from WT-such as the XBB variant-and this concerning situation could be mitigated by a second Omicron booster. Similarly, in humans, repeated Omicron infections could alleviate WT vaccination-induced immune imprinting and generate broad neutralization responses in both plasma and nasal mucosa. Notably, deep mutational scanning-based epitope characterization of 781 receptor-binding domain (RBD)-targeting monoclonal antibodies isolated from repeated Omicron infection revealed that double Omicron exposure could induce a large proportion of matured Omicron-specific antibodies that have distinct RBD epitopes to WT-induced antibodies. Consequently, immune imprinting was largely mitigated, and the bias towards non-neutralizing epitopes observed in single Omicron exposures was restored. On the basis of the deep mutational scanning profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated that these mutations could further boost the immune-evasion capability of XBB.1.5 while maintaining high ACE2-binding affinity. Our findings suggest that the WT component should be abandoned when updating COVID-19 vaccines, and individuals without prior Omicron exposure should receive two updated vaccine boosters.

XBB.1.5 spike protein COVID-19 vaccine induces broadly neutralizing and cellular immune responses against EG.5.1 and emerging XBB variants

Monovalent SARS-CoV-2 Prototype (Wuhan-Hu-1) and bivalent (Prototype + BA.4/5) COVID-19 vaccines have demonstrated a waning of vaccine-mediated immunity highlighted by lower neutralizing antibody responses against SARS-CoV-2 Omicron XBB sub-variants. The reduction of humoral immunity due to the rapid evolution of SARS-CoV-2 has signaled the need for an update to vaccine composition. A strain change for all authorized/approved vaccines to a monovalent composition with Omicron subvariant XBB.1.5 has been supported by the WHO, EMA, and FDA. Here, we demonstrate that immunization with a monovalent recombinant spike protein COVID-19 vaccine (Novavax, Inc.) based on the subvariant XBB.1.5 induces neutralizing antibodies against XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1, and XBB.1.16.6 subvariants, promotes higher pseudovirus neutralizing antibody titers than bivalent (Prototype + XBB.1.5) vaccine, induces SARS-CoV-2 spike-specific Th1-biased CD4 + T-cell responses against XBB subvariants, and robustly boosts antibody responses in mice and nonhuman primates primed with a variety of monovalent and bivalent vaccines. Together, these data support updating the Novavax vaccine to a monovalent XBB.1.5 formulation for the 2023–2024 COVID-19 vaccination campaign.

Public Perception of the Chemical Composition of Covid-19 Vaccine that Hinders the Implementations of COVID-19 Vaccination in Indonesia

Indonesia has been facing COVID-19 since March 2020, causing significant problems for public health. Indonesia is trying to solve this problem, and the vaccination program began in January 2021. Several obstacles include public acceptance of the composition of the COVID-19 vaccine. We systematically searched peer-reviewed studies during 2020-2022, examining analyses of the Chemical Composition of the COVID-19 Vaccine authorized in Indonesia. We also explored the related information from the official body. Finally, we constructed a short review of the public acceptance of the vaccine focusing on the chemical composition. All COVID-19 vaccines are intended to induce humoral and cellular immunity toward infection. The antigen causes this as an active ingredient of the vaccine. The vaccine also contains adjuvants, and some other chemicals are required. The expansion aims to maintain the content of the vaccine, strengthen the body's reaction to the vaccine, and facilitate the administration process. But there are concerns about the risk of unintended effects of the substances used. This perception includes those that hinder the implementation of COVID-19 Vaccination in Indonesia. There is a need to disseminate information and education about the vaccine composition so that the optimal vaccination program benefits the community.