Monovalent Vaccine Research Articles

Divergence of variant antibodies following SARS-CoV-2 booster vaccines in myeloma and impact of hybrid immunity

Hematological malignancies are associated with an increased risk of complications during SARS-CoV-2 infections. Primary series or monovalent booster vaccines reduce disease severity, hospitalization, and death among multiple myeloma patients. We characterized virus-neutralizing and spike-binding antibody profiles following monovalent (WA1) or bivalent (WA1/BA.5) SARS-CoV-2 booster vaccination in MM patients. Bivalent vaccination improved the breadth of binding antibodies but not neutralization activity against contemporary variants. Hybrid immunity and immune imprinting impact vaccine-elicited immunity.

Vaccination against respiratory syncytial virus (RSV)-For the protection of infants and older adults

Respiratory syncytial virus (RSV) is afrequent cause of respiratory infections in all age groups. Infections in infants and older adults frequently result in severe disease and complications. There is no specific antiviral treatment against RSV. The characterization of the structure of the fusion (F) protein in its immunogenic prefusion conformation has enabled the development of novel vaccines directed against the prefusion protein as the antigen. These include an adjuvanted monovalent vaccine (Arexvy) and anonadjuvanted bivalent vaccine (Abrysvo). Both are approved and indicated for use in older adults, in whom they have been shown to be over 80% effective in the protection against symptomatic RSV infections and associated lower respiratory tract diseases. Abrysvo is approved for use in pregnancy to protect the newborn through the transplacental transfer of high-titer maternal antibodies. The vaccine has been shown to have an efficacy of over 80% in the first 3 months of life to protect the infant from severe RSV-associated lower respiratory disease but slightly deceases after an age of 6 months. The clinical studies demonstrated the safety of the vaccines in both adults and pregnant women. The rate of undesired side effects was low in all studies and severe side effects were very rare. The new vaccines are efficacious new tools to prevent RSV-associated disease and complications in high-risk groups. For infants, an alternative strategy can be passive immunization with monoclonal antibodies, including the recently developed nirsevimab, which has also shown high efficacy.

Comparative Analysis of the Neutralizing Capacity of Monovalent and Bivalent Formulations of Betuvax-CoV-2, a Subunit Recombinant COVID-19 Vaccine, Against Various Strains of SARS-CoV-2

SARS-CoV-2, the causal agent of the COVID-19 pandemic, is characterized by rapid evolution, which poses a significant public health challenge. Effective vaccines that provide robust protection, elicit strong immune responses, exhibit favorable safety profiles, and enable cost-effective large-scale production are crucial. The RBD-Fc-based Betuvax-CoV-2 vaccine has previously demonstrated a favorable safety profile and induced a significant anti-SARS-CoV-2 humoral immune response in clinical trials. Due to the rapid evolution and emergence of new SARS-CoV-2 strains, the relevance of bivalent vaccine formulations has increased. Methods: This study compared the neutralizing capacity of monovalent and bivalent vaccine formulations against different SARS-CoV-2 strains detected with a SARS-CoV-2 microneutralization assay (MNT). Findings: The monovalent Wuhan-based vaccine generated neutralizing antibodies against the Wuhan and Omicron BA.2 variants but not the distinct Omicron BQ.1 strain. Conversely, the monovalent BA.2-based vaccine induced neutralizing antibodies against both Omicron strains but not Wuhan. While the bivalent Wuhan and BA.2-based vaccine was effective against strains containing the same antigens, it was insufficient to neutralize the distinctive BQ.1 strain at a small dosage. Interpretation: These findings suggest that the vaccine composition should closely match the circulating SARS-CoV-2 strain to elicit the optimal neutralizing antibody response and include the appropriate dosage. Moreover, this study did not find additional advantages of using the bivalent form over the monovalent form for the vaccination against a single prevailing SARS-CoV-2 strain.

Cellular and humoral immunity and IgG subclass distribution after omicron XBB.1.5 monovalent vaccination in Japan

BackgroundUp to seven doses of coronavirus disease 2019 (COVID-19) mRNA vaccines (BNT162b2) were administered to Japanese healthcare workers, until February 2024. The monovalent Omicron XBB.1.5 vaccine (hereafter called XBB.1.5 vaccine) was used for dose 7. ObjectiveAlthough the XBB.1.5 vaccine has been reported to induce a robust increase in neutralizing antibodies against the currently circulating Omicron variant BA.2.86, little is known about its serological effects in Japan, where the BNT162b2 mRNA vaccine is the most frequently administered in the world. Study designTwenty-five recipients of the XBB.1.5 vaccine, categorized as seronegative (n = 18) or seropositive (n = 7) based on their recent history of COVID-19, were analyzed. Neutralizing antibody titers against Omicron subvariants, receptor binding domain (RBD) IgG levels, IgG subclass distribution, and T-cell responses were assessed. ResultsWe found a significant increase in neutralizing antibody titers against XBB.1.5 and BA.2.86 variants following XBB.1.5 vaccination, particularly in seropositive individuals. No significant change in total RBD IgG levels was observed, indicating efficient induction of antibodies targeting regions outside the RBD by XBB.1.5 vaccination. IgG subclass analysis demonstrated no significant subclass switching after vaccination. T-cell responses against the virus were comparable between seropositive and seronegative groups. ConclusionsThe study suggests that XBB.1.5 vaccination enhances humoral immunity against Omicron variants without significant IgG subclass switching. However, some individuals with low pre-vaccination IgG titers did not exhibit increased antibody levels post-vaccination, raising concerns about potential immune tolerance.

Effectiveness of the original monovalent mRNA COVID-19 vaccination series against hospitalization for COVID-19-associated venous thromboembolism.

COVID-19 is a strong risk factor for venous thromboembolism (VTE). Few studies have evaluated the effectiveness of COVID-19 vaccination in preventing hospitalization for COVID-19 with VTE. Adults hospitalized at 21 sites between March 2021 and October 2022 with symptoms of acute respiratory illness were assessed for COVID-19, completion of the original monovalent mRNA COVID-19 vaccination series, and VTE. Prevalence of VTE was compared between unvaccinated and vaccinated patients with COVID-19. Vaccine effectiveness in preventing COVID-19 hospitalization with VTE was calculated using a test negative design. Vaccine effectiveness was also stratified by predominant circulating SARS-CoV-2 variant. Among 18,811 patients (median age 63 [IQR:50-73], 49% women, 59% non-Hispanic White, 20% non-Hispanic Black, 14% Hispanic, and median of 2 comorbid conditions [IQR:1-3]), 9,792 were admitted with COVID-19 (44% vaccinated) and 9,019 were test-negative controls (73% vaccinated). Among patients with COVID-19, 601 were diagnosed with VTE by hospital day 28, of whom 170 were vaccinated. VTE was more common among unvaccinated than vaccinated COVID-19 patients (7.8% versus 4.0%; p=0.001). Vaccine effectiveness against COVID-19 hospitalization with VTE was 84% (95% CI: 80-87%) overall. Vaccine effectiveness stratified by predominant circulating variant was 88% (73-95%) for alpha, 93% (90-95%) for delta, and 68% (58-76%) for omicron variants. Vaccination with the original monovalent mRNA series was associated with a decrease in COVID-19 hospitalization with VTE, though data detailing prior history of VTE and use of anticoagulation were not available. These findings will inform risk-benefit considerations for those considering vaccination.

Long-term outcomes of high-risk human papillomavirus in anal infection support HPV men vaccination

Abstract Introduction/Objective The clinical laboratory in a local hospital has an important role in population surveillance. The clinical laboratory performs analyses on patients admitted to the hospital as inpatients or critical patients and it is also a reference point for people’s health check-ups and health surveillance. Infectious diseases normally have severe symptoms. To ensure benefits from therapeutic treatment, a timely diagnosis is necessary. The human papillomavirus (HPV) virus is among the most diagnosed sexually transmitted infections worldwide, and the male gender is not exempt from it. In fact, 1 out of 3 male individuals is infected with HPV and 1 out of 5 male individuals is infected with a high-risk strain (1). In Italy, vaccination is underway for women only. Vaccine prevention extended to male individuals could lead to a halving of HPV cases. Methods/Case Report From 2018 to 2022, we performed 7362 HPV tests using DNA extraction technique (QiaSimphony) and real-time Multiplex PCR (SeeGene 28 strains). Results (if a Case Study enter NA) 3762 out of 7362 HPV tests performed were positive for one (2059 patients) or more (1969 patients) HPV strains. Women, who are more aware of prevention, are more represented in our sample of subjects. The tests performed on women are 6499 and half (3331) are positive for at least one strain of HPV. Regarding men, 863 tests were performed. About half (431 patients) were positive for at least one HPV strain. Noteworthy, out of 175 anal HPV tests, 48% were positive and 1 patient had squamous cell carcinoma. Furthermore, in our male patients tested 2 - 12% had low or medium-risk injuries. In total, out of 7529 tests carried out from 2018 to 2022, over than 50% were found to be high-risk viral strains (5231). Of these, however, approximately half (2781) are now preventable with the monovalent HPV vaccine (strains covered: 6, 11, 16, 18, 31, 33, 45, 52, 58). Conclusion The Ospedale Isola Tiberina – Gemelli Isola is an Institution in the center of Rome, Italy. It is also a reference center for birthrates and women’s prevention. Therefore, our Institution is very efficient in raising awareness of the prevention of HPV-related cancer. Current data indicate that male cases are not negligible, being positive in almost 50% of anal tests, and associated with an increased risk of the related cancers. These data can have an important impact on the Italian population, both in terms of the spread of HPV and healthcare burden and in terms of high healthcare costs.

Broad immunogenicity to prior SARS-CoV-2 strains and JN.1 variant elicited by XBB.1.5 vaccination in nursing home residents.

SARS-CoV-2 vaccination has reduced hospitalization and mortality for nursing home residents (NHRs) but emerging variants and waning immunity challenge vaccine effectiveness. This study assesses the immunogenicity of the most recent XBB.1.5 monovalent vaccine to variant strains among NHRs. Participants were subset of a longitudinal study of consented NHRs and Healthcare workers (HCWs) who have received serial blood draws to assess immunogenicity with each SARS-CoV-2 mRNA vaccine dose. We report data on participants who received the XBB.1.5 monovalent vaccine post-FDA approval in Fall 2023. NHRs were categorized by whether they had an interval SARS-CoV-2 infection between their first bivalent vaccine dose and their XBB.1.5 monovalent vaccination. The sample included 61 NHRs [median age 76 (IQR 68-86), 51% female] and 28 HCWs [median age 45 (IQR 31-58), 46% female). After XBB.1.5 vaccination, a robust geometric mean fold rise (GMFR) in XBB.1.5-specific neutralizing antibody titers was observed:17.3 (95% confidence interval [CI] 9.3, 32.4) and NHRs with interval infection and 11.3 (95% CI 5, 25.4) in those without and 13.6 (95% CI 8.4,22) in HCWs. For JN.1-specific titers, GMFRs were 14.9 (95% CI 7.9, 28) and 6.5 (95% CI 3.3, 13.1) in NHRs with and without interval infection, and 11.4 (95% CI 6.2, 20.9) in HCWs. NHRs with interval SARS-CoV-2 infection had higher titers across all analyzed strains analyzed. The XBB.1.5 vaccine significantly elevates Omicron-specific neutralizing antibody titers to XBB.1.5 and JN.1 strains in both NHRs and HCWs with more pronounced in those previously infected with SARS-CoV-2 since bivalent vaccination.

Preclinical immunogenicity and safety of hemagglutinin-encoding modRNA influenza vaccines

Seasonal epidemics of influenza viruses are responsible for a significant global public health burden. Vaccination remains the most effective way to prevent infection; however, due to the persistence of antigenic drift, vaccines must be updated annually. The selection of vaccine strains occurs months in advance of the influenza season to allow adequate time for production in eggs. RNA vaccines offer the potential to accelerate production and improve efficacy of influenza vaccines. We leveraged the nucleoside-modified RNA (modRNA) platform technology and lipid nanoparticle formulation process of the COVID-19 mRNA vaccine (BNT162b2; Comirnaty®) to create modRNA vaccines encoding hemagglutinin (HA) (modRNA-HA) for seasonal human influenza strains and evaluated their preclinical immunogenicity and toxicity. In mice, a monovalent modRNA vaccine encoding an H1 HA demonstrated robust antibody responses, HA-specific Th1-type CD4+ T cell responses, and HA-specific CD8+ T cell responses. In rhesus and cynomolgus macaques, the vaccine exhibited durable functional antibody responses and HA-specific IFN-γ+ CD4+ T cell responses. Immunization of mice with monovalent, trivalent, and quadrivalent modRNA-HA vaccines generated functional antibody responses targeting the seasonal influenza virus(es) encoded in the vaccines that were greater than, or similar to, those of a licensed quadrivalent influenza vaccine. Monovalent and quadrivalent modRNA-HA vaccines were well-tolerated by Wistar Han rats, with no evidence of systemic toxicity. These nonclinical immunogenicity and safety data support further evaluation of the modRNA-HA vaccines in clinical studies.

Determination of T cell response against XBB variants in adults who received either monovalent wild type inactivated whole virus or mRNA vaccine or bivalent WT/BA.4-5 COVID-19 mRNA vaccine as the additional booster

ObjectivesAs the SARS-CoV-2 virus evolves more rapidly than vaccines are updated, T cell immunity potentially confers protection against disease progression and death from new variants. In this study, we aimed to assess whether the current boosting vaccination schemes offer sufficient T cell protection against new SARS-CoV-2 variants. Methods. 292 adults who had received the second booster of either monovalent wild type vaccines (inactivated virus or mRNA) (cohort 1) or the second/third booster of bivalent WT/BA.4-5 mRNA vaccine (cohort 2) were recruited in Hong Kong. All participants showed no serological evidence of recent infection of SARS-CoV-2. Blood samples of each participant were collected before and one-month after receiving the booster. T cell and antibody responses were determined by flow cytometry and neutralization test respectively. Results. Among all vaccination strategies, only the adults who had received the bivalent vaccine as the third booster dose significantly elicited T cell responses to the XBB variant. Either monovalent or bivalent mRNA but not inactivated virus vaccine as the second/third booster induced antibody against different XBB variants. Conclusions. Receiving bivalent mRNA vaccine as the third booster is preferrable to induce both T cell and antibody responses against XBB.

Enhancing Omicron Sublineage Neutralization: Insights From Bivalent and Monovalent COVID-19 Booster Vaccines and Recent SARS-CoV-2 Omicron Variant Infections.

Omicron variants have rapidly diversified into sublineages with mutations that enhance immune evasion, posing challenges for vaccination and antibody responses. This study aimed to compare serum cross-neutralizing antibody responses against various SARS-CoV-2 Omicron sublineages (BA.1, BA.5, XBB.1.17.1, FK.1.1, and JN.1) in recipients of monovalent COVID-19 boosters, bivalent booster recipients, and individuals who had recovered from Omicron BA.5 infections. We conducted a micro-neutralization assay on serum samples from monovalent BNT162b2 booster recipients (N = 54), bivalent BNT162b2 booster recipients (N = 24), and SARS-CoV-2 Omicron BA.5-recovered individuals (N = 13). The history of SARS-CoV-2 Omicron infection was assessed using ELISA against the SARS-CoV-2 NP protein. Bivalent booster recipients exhibited significantly enhanced neutralization efficacy against Omicron sublineages compared to those who had received monovalent booster vaccinations. Omicron BA.5-recovered individuals displayed similar neutralizing antibodies (NAbs) to the bivalent booster recipients. Despite the improved neutralization in bivalent recipients and BA.5-recovered individuals, there were limitations in neutralization against the recently emerged Omicron subvariants: XBB.1.17.1 FK.1.1, and JN.1. In both monovalent and bivalent booster recipients, a history of Omicron breakthrough infection was associated with relatively higher geometric mean titers of NAbs against Omicron BA.1, BA.5, and XBB.1.17.1 variants. This study underscores the intricate interplay between vaccination strategies, immune imprinting, and the dynamic landscape of SARS-CoV-2 variants. Although bivalent boosters enhance neutralization, addressing the challenge of emerging sublineages like XBB.1.17.1, FK.1.1, and JN.1 may necessitate the development of tailored vaccines, underscoring the need for ongoing adaptation to effectively combat this highly mutable virus.

Detection of PCV2d in Vaccinated Pigs in Colombia and Prediction of Vaccine T Cell Epitope Coverage against Circulating Strains Using EpiCC Analysis.

Porcine circovirus type 2 (PCV2) is strongly linked to a group of syndromes referred to as porcine-circovirus-associated diseases (PCVADs), which are controlled through vaccination; however, this does not induce sterilizing immunity but is instead involved in the evolution of the virus and is considered a factor in vaccine failure. This study sampled 84 herds (167 pigs) vaccinated against PCV2 and with clinical signs of PCVADs in five provinces across Colombia. PCV2 was identified and further characterized at the molecular level via genotyping and phylogenetic reconstructions. In addition, PCV2-associated lesions were examined via histopathology. Furthermore, the PCV2-Cap sequences retrieved were compared with three vaccines via the EpiCC tool and T cell epitope coverage. The prevalence of PCV2 was 82% in pigs and 92.9% in herds. The highest viral loads were identified in lymphoid tissue, and PCV2d emerged as the most predominant in pigs and herds (93.4% and 92.3%). Sequences for PCV2-ORF2 (n = 57; 55 PCV2d and 2 PCV2a) were determined, and PCV2d sequences were highly similar. The most common pneumonia pattern was suppurative bronchopneumonia, while the most common lung lesion was exudation in the airways; in lymphoid tissue, there was lymphoid depletion. The bivalent vaccine (PCV2a and PCVb) exhibited a higher EpiCC score (8.36) and T cell epitope coverage (80.6%) than monovalent PCV2a vaccines. In conclusion, PCV2d currently circulates widely in Colombia. Despite vaccination, there are clinical cases of PCV2, and immunoinformatic analyses demonstrate that bivalent vaccines improved the average coverage.

Symptoms Six Weeks After COVID-19 Are Reduced Among US Health Care Personnel Receiving Additional Vaccine Doses During the Omicron Period, December 2021-April 2022.

The objective of this study was to test the hypothesis that subsequent doses of the coronavirus disease 2019 (COVID-19) vaccine are associated with lower incidence of COVID-19-like symptoms at 6 weeks after infection. This study was a case-control analysis of health care personnel in an ongoing multicenter COVID-19 vaccine effectiveness study. We enrolled participants at the time of COVID-19-like symptoms between December 19, 2021, and April 27, 2022, which corresponded to the early Omicron-predominant period after original monovalent severe acute respiratory syndrome coronavirus 2 additional vaccination doses became available. Our outcome was self-reported symptoms completed 6 weeks after the onset of symptoms. We enrolled 2478 participants, of whom 1422 (57%) had COVID-19. The prevalence of symptoms at 6 weeks was 26% (n = 373) in those with COVID-19 and 18% (n = 195) in those without COVID-19. Fatigue (11%) and difficulty sleeping (7%) were most strongly associated with COVID-19. A total of 1643 (66%) participants received a subsequent vaccine dose (after the primary series). Participants with COVID-19 who had received a subsequent vaccination had lower odds of symptoms at 6 weeks (adjusted odds ratio [aOR], 0.55; 95% CI, 0.43-0.70), but this relationship was not observed in those without COVID-19 (aOR, 0.87; 95% CI, 0.59-1.29). Health care personnel who received subsequent doses of original monovalent COVID-19 vaccine had a lower prevalence of symptoms at 6 weeks than those that did not.

Evaluation of a Quadrivalent Shigella flexneri Serotype 2a, 3a, 6, and Shigella sonnei O-Specific Polysaccharide and IpaB MAPS Vaccine

Background: Shigellosis is the leading cause of diarrheal deaths worldwide and is particularly dangerous in children under 5 years of age in low- and middle-income countries. Additionally, the rise in antibiotic resistance has highlighted the need for an effective Shigella vaccine. Previously, we have used the Multiple Antigen-Presenting System (MAPS) technology to generate monovalent and quadrivalent Salmonella MAPS vaccines that induce functional antibodies against Salmonella components. Methods: In this work, we detail the development of several monovalent vaccines using O-specific polysaccharides (OSPs) from four dominant serotypes, S. flexneri 2a, 3a, and 6, and S. sonnei. We tested several rhizavidin (rhavi) fusion proteins and selected a Shigella-specific protein IpaB. Quadrivalent MAPS were made with Rhavi-IpaB protein and tested in rabbits for immunogenicity. Results: Individual MAPS vaccines generated robust, functional antibody responses against both IpaB and the individual OSP component. Antibodies to IpaB were effective across Shigella serotypes. We also demonstrate that the OSP antibodies generated are specific to each homologous Shigella O type by performing ELISA and bactericidal assays. We combined the components of each MAPS vaccine to formulate a quadrivalent MAPS vaccine which elicited similar antibody and bactericidal responses compared to their monovalent counterparts. Finally, we show that the quadrivalent MAPS immune sera are functional against several clinical isolates of the serotypes used in the vaccine. Conclusions: This quadrivalent MAPS Shigella vaccine is immunogenicity and warrants further study.

Persistence of hepatitis B surface antibody until 7 years of age following administration of hexavalent and pentavalent vaccines in children at 2, 4, 6, and 18 months

Thailand incorporated the hepatitis B (HepB) vaccine into the infant combination vaccine known as pentavalent wP-containing vaccines (DTwP-HB-Hib) and hexavalent aP-containing vaccines (DTaP-IPV-HB-Hib). We followed healthy children from the clinical trial (ClinicalTrials.gov NCT02408926) in which children were randomly assigned to receive either pentavalent or hexavalent vaccines for their primary series (administered at 2, 4, and 6 months) and first booster vaccination (at 18 months), following the monovalent HepB vaccine at birth. Blood samples were collected to evaluate the persistence of hepatitis B surface antibody (anti-HBs) at 3, 4, 5, 6 and 7 years of age. The results showed that at 7 years of age, a higher percentage of children in the hexavalent group maintained anti-HBs levels ≥ 10 mIU/mL compared to those in the pentavalent group (86.9 % vs. 59.7 %). This study showed good persistence of anti-HBs among hexavalent-vaccinated children 5.5 years after the last dose of the HepB vaccine.

Indirect effectiveness of COVID-19 vaccines in the pre-omicron and omicron periods: A nation-wide test-negative case-control study in Brazil

ObjectivesMass COVID-19 immunization campaigns altered the pandemic's progress by protecting the vaccine recipient and reducing transmission. However, evidence for indirect vaccine effectiveness (IVE) is limited due to the difficulties of ascertaining this type of protection. MethodsUsing linked national Brazilian databases, we adapted the test-negative design to evaluate the IVE against symptomatic infection. We analyzed data from January 1 to December 1, 2021 (pre-omicron) and January 1 to April 30, 2022 (omicron BA.1 and BA.2). We compared the probability of testing positive across various levels of second ancestral-strain monovalent COVID-19 vaccine dose coverage, including only unvaccinated individuals in the main analysis and both vaccinated and unvaccinated individuals in additional analyses. Sensitivity analysis focused on children younger than 12 years who did not have access to COVID-19 vaccines during the pre-omicron period. ResultsWe included 11,039,315 unvaccinated individuals tested during the pre-omicron study period. IVE was minimal until 30% vaccination coverage (<10%), then it followed a dose-dependent pattern, peaking at 37.7 (95% confidence interval 32-42.8) at 70% coverage. For children younger than 12 years, IVE peaked at 59.8% (95% confidence interval 52.7-65.9) at 70% coverage. During the omicron period, IVE remained constant at about 5% across all comparisons. ConclusionsOur findings confirm that high vaccination coverage using vaccines that prevent infection indirectly protects the community. However, IVE was substantially higher during the pre-omicron period.

Ipsilateral or contralateral boosting of mice with mRNA vaccines confers equivalent immunity and protection against a SARS-CoV-2 Omicron strain.

Boosting with mRNA vaccines encoding variant-matched spike proteins has been implemented to mitigate their reduced efficacy against emerging SARS-CoV-2 variants. Nonetheless, in humans, it remains unclear whether boosting in the ipsilateral or contralateral arm with respect to the priming doses impacts immunity and protection. Here, we boosted K18-hACE2 mice with either monovalent mRNA-1273 (Wuhan-1 spike) or bivalent mRNA-1273.214 (Wuhan-1 + BA.1 spike) vaccine in the ipsilateral or contralateral leg after a two-dose priming series with mRNA-1273. Boosting in the ipsilateral or contralateral leg elicited equivalent levels of serum IgG and neutralizing antibody responses against Wuhan-1 and BA.1. While contralateral boosting with mRNA vaccines resulted in the expansion of spike-specific B and T cells beyond the ipsilateral draining lymph node (DLN) to the contralateral DLN, administration of a third mRNA vaccine dose at either site resulted in similar levels of antigen-specific germinal center B cells, plasmablasts/plasma cells, T follicular helper cells, and CD8+ T cells in the DLNs and the spleen. Furthermore, ipsilateral and contralateral boosting with mRNA-1273 or mRNA-1273.214 vaccines conferred similar homologous or heterologous immune protection against SARS-CoV-2 BA.1 virus challenge with equivalent reductions in viral RNA and infectious virus in the nasal turbinates and lungs. Collectively, our data show limited differences in B and T cell immune responses after ipsilateral and contralateral site boosting by mRNA vaccines that do not substantively impact protection against an Omicron strain.IMPORTANCESequential boosting with mRNA vaccines has been an effective strategy to overcome waning immunity and neutralization escape by emerging SARS-CoV-2 variants. However, it remains unclear how the site of boosting relative to the primary vaccination series shapes optimal immune responses or breadth of protection against variants. In K18-hACE2 transgenic mice, we observed that intramuscular boosting with historical monovalent or variant-matched bivalent vaccines in the ipsilateral or contralateral limb elicited comparable levels of serum spike-specific antibody and antigen-specific B and T cell responses. Moreover, boosting on either side conferred equivalent protection against a SARS-CoV-2 Omicron challenge strain. Our data in mice suggest that the site of intramuscular boosting with an mRNA vaccine does not substantially impact immunity or protection against SARS-CoV-2 infection.

Use of Haemophilus influenzae Type b-Containing Vaccines Among American Indian and Alaska Native Infants: Updated Recommendations of the Advisory Committee on Immunization Practices - United States, 2024.

Invasive Haemophilus influenzae type b (Hib) disease is a serious bacterial infection that disproportionally affects American Indian and Alaska Native (AI/AN) populations. Hib vaccination with a monovalent Hib conjugate vaccine consisting of Hib capsular polysaccharide (polyribosylribitol phosphate [PRP]) conjugated to outer membrane protein complex of Neisseria meningitidis serogroup B, PRP-OMP (PedvaxHIB, Merck and Co., Inc.) has historically been preferred for AI/AN infants, who are at increased risk for invasive Hib disease, because it provides substantial protection after the first dose. On June 26, 2024, CDC's Advisory Committee on Immunization Practices (ACIP) recommended that a hexavalent, combined diphtheria and tetanus toxoids and acellular pertussis (DTaP), inactivated poliovirus (IPV), Hib conjugate, and hepatitis B (HepB) vaccine, DTaP-IPV-Hib-HepB (Vaxelis, MSP Vaccine Company) should be included with monovalent PRP-OMP in the preferential recommendation for AI/AN infants because of the PRP-OMP Hib component. A primary Hib vaccination series consisting of either 1) monovalent PRP-OMP (2-dose series at ages 2 and 4 months) or 2) DTaP-IPV-Hib-HepB (3-dose series at ages 2, 4, and 6 months) is preferred for AI/AN infants. DTaP-IPV-Hib-HepB is only indicated for use in infants at ages 2, 4, and 6 months and should not be used for the booster doses of Hib, DTaP, or IPV vaccines. For the booster dose of Hib vaccine, no vaccine formulation is preferred for AI/AN children; any Hib vaccine (except DTaP-IPV-Hib-HepB) should be used. This report summarizes evidence considered for these recommendations and provides clinical guidance for the use of Hib-containing vaccines among AI/AN infants and children.

Neutralization and Stability of JN.1-derived LB.1, KP.2.3, KP.3 and KP.3.1.1 Subvariants.

During the summer of 2024, COVID-19 cases surged globally, driven by variants derived from JN.1 subvariants of SARS-CoV-2 that feature new mutations, particularly in the N-terminal domain (NTD) of the spike protein. In this study, we report on the neutralizing antibody (nAb) escape, infectivity, fusion, and stability of these subvariants-LB.1, KP.2.3, KP.3, and KP.3.1.1. Our findings demonstrate that all of these subvariants are highly evasive of nAbs elicited by the bivalent mRNA vaccine, the XBB.1.5 monovalent mumps virus-based vaccine, or from infections during the BA.2.86/JN.1 wave. This reduction in nAb titers is primarily driven by a single serine deletion (DelS31) in the NTD of the spike, leading to a distinct antigenic profile compared to the parental JN.1 and other variants. We also found that the DelS31 mutation decreases pseudovirus infectivity in CaLu-3 cells, which correlates with impaired cell-cell fusion. Additionally, the spike protein of DelS31 variants appears more conformationally stable, as indicated by reduced S1 shedding both with and without stimulation by soluble ACE2, and increased resistance to elevated temperatures. Molecular modeling suggests that the DelS31 mutation induces a conformational change that stabilizes the NTD and strengthens the NTD-Receptor-Binding Domain (RBD) interaction, thus favoring the down conformation of RBD and reducing accessibility to both the ACE2 receptor and certain nAbs. Additionally, the DelS31 mutation introduces an N-linked glycan modification at N30, which shields the underlying NTD region from antibody recognition. Our data highlight the critical role of NTD mutations in the spike protein for nAb evasion, stability, and viral infectivity, and suggest consideration of updating COVID-19 vaccines with antigens containing DelS31.

A Third COVID-19 Vaccine Dose in Kidney Transplant Recipients Induces Antibody Response to Vaccine and Omicron Variants but Shows Limited Ig Subclass Switching.

This study addresses the challenges faced by kidney transplant recipients (KTRs) in mounting effective immune responses against COVID-19. By evaluating the antibody responses to a third dose of monovalent mRNA COVID-19 vaccine and its effectiveness against Omicron subvariants (BA.1 and BA.5), this study reveals significant reductions in both binding and neutralizing antibodies in KTRs compared to healthy controls. The research highlights altered IgG subclass switching and heterogeneous responses within the KTR population. Reduced recognition of variants, coupled with differences in IgG subclasses, decreases both the quality and quantity of protective antibodies after vaccination in KTRs. These findings underscore the need for tailored vaccination strategies for immunosuppressed populations such as KTRs. Alternative formulations and doses of COVID-19 vaccines should be considered for people with severely compromised immune systems, as more frequent vaccinations may not significantly improve the response, especially regarding neutralizing antibodies.

Effectiveness and impact of monovalent rotavirus vaccination in Afghanistan: a test-negative case–control analysis

Afghanistan introduced monovalent rotavirus vaccine (Rotarix) into its national immunisation schedule in January, 2018. While post-licensure studies have shown substantial declines in rotavirus gastroenteritis cases and deaths globally, there is little evidence of rotavirus vaccine effectiveness and impact from low-income countries in Asia. We aimed to evaluate the effectiveness of the Rotarix vaccine and the impact of Rotarix vaccine on rotavirus gastroenteritis hospitalisations (ie, hospital admissions) among children younger than 5 years in Afghanistan. We used a test-negative case-control design embedded in an active sentinel surveillance platform to evaluate vaccine effectiveness. Children born on or after Jan 1, 2018, who had documentation of their rotavirus vaccination status and who were admitted for acute gastroenteritis at one of four sentinel hospitals from May, 2018 to December, 2021 were eligible to be included. We used an unconditional logistic regression model to estimate vaccine effectiveness and 95% CIs for a complete series of doses compared with no rotavirus vaccine doses among patients admitted with acute gastroenteritis. Vaccine effectiveness against hospitalisation was calculated as (1 - [odds of being vaccinated in cases] / [odds of being vaccinated in controls]) × 100%. We compared pre-vaccine (2013-15) and post-vaccine (2019-21) surveillance data from two sites to calculate vaccine impact. The vaccine effectiveness analysis included 1172 cases and 2173 controls. Approximately 2108 (63·0%) of 3345 cases and controls were male, 1237 (37·0%) were female, and 2171 (65·0%) were aged 6-11 months. Two doses of Rotarix were 45% (95% CI 22-62) effective against rotavirus hospitalisation in children aged 6-59 months, adjusting for age, severity, admission year, and rotavirus season. Rotavirus positivity decreased from 51% pre-vaccine to 39% post-vaccine, resulting in a 39% adjusted reduction in rotavirus positivity among children younger than 5 years admitted with acute gastroenteritis. Rotarix showed moderate effectiveness in preventing rotavirus gastroenteritis hospitalisations, consistent with findings in other low-income countries. These findings support the continued administration of the rotavirus vaccine in Afghanistan. Gavi, the Vaccine Alliance. For the Dari translation of the abstract see Supplementary Materials section.