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Vaccine[JOURNAL]

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Apples and oranges: Better harmonisation of vaccine trials is needed to inform inclusion in immunisation programs.

Marcato AJ, Campbell PT, Spirkoska V … +4 more , Ainslie KEC, Carlin JB, Price DJ, Carville KS

Vaccine · 2026 Jul · PMID 42119391 · Publisher ↗

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Strategies to enhance DNA vaccine efficacy against emerging arboviruses: lessons from ZIKA and Chikungunya viruses.

Sreekanth S, Lahon A

Vaccine · 2026 Jul · PMID 42119390 · Publisher ↗

The mosquito-borne arboviruses Zika and Chikungunya pose serious health threats worldwide, often co-circulating and causing co-infections in Aedes endemic regions. While no licensed vaccine is currently available for Zik... The mosquito-borne arboviruses Zika and Chikungunya pose serious health threats worldwide, often co-circulating and causing co-infections in Aedes endemic regions. While no licensed vaccine is currently available for Zika virus (ZIKV), recent progress has led to the approval of vaccines for Chikungunya virus (CHIKV) in few countries, highlighting the need for improved vaccine strategies. Zika virus (ZIKV) presents unique challenges, including its neurotropism, association with congenital abnormalities, and potential for sexual and vertical transmission, whereas Chikungunya virus (CHIKV) is characterized by viral persistence in joint-associated tissues, leading to chronic inflammatory manifestations such as long-term arthralgia, along with comparatively limited clinical trial data for vaccine candidates. DNA vaccines offer a promising platform since they are safe and easy to produce; but their immunogenicity in humans is limited. The rational use of adjuvants and optimized delivery systems is important for enhancing DNA vaccine efficacy. This review discusses current adjuvant classes, including Toll-like receptor (TLR) agonists, molecular adjuvants, and classical adjuvants, focusing on their mechanisms to enhance immune cell activation and adaptive immunity. We summarize preclinical and clinical findings on DNA vaccines for ZIKV and CHIKV, highlighting the synergy of adjuvants with different delivery technologies and discuss the rationale for multivalent DNA vaccine strategies to address co-circulating arboviral infections. Finally, we have identified research gaps and suggested a translational roadmap to accelerate the development of effective DNA vaccines against these emerging arboviruses.

Modeling optimal deployment strategies for Nipah vaccines and monoclonal antibodies.

Cortes-Azuero O, Vegvari C, Sutcliffe E … +6 more , Roney E, Scarponi D, Mukandavire C, Cauchemez S, Gurley E, Salje H

Vaccine · 2026 Jun · PMID 42119335 · Publisher ↗

Nipah virus (NiV) is endemic in Pteropus bats across South and Southeast Asia. Spillover into human populations results in usually fatal disease with the potential for human-to-human spread, which has led to NiV being cl... Nipah virus (NiV) is endemic in Pteropus bats across South and Southeast Asia. Spillover into human populations results in usually fatal disease with the potential for human-to-human spread, which has led to NiV being classified by WHO as a priority pathogen. NiV vaccines and monoclonal antibodies (mAbs) are in development. However, it remains unclear how these medical countermeasures could be used most effectively. Here, we consider three different outbreak scenarios: limited, short-lived outbreaks as seen almost annually in Bangladesh and India; livestock amplified outbreaks as seen in Malaysia in 1998; and a third theoretical scenario of an extended outbreak caused by an evolved NiV strain with increased transmissibility. For each scenario, we considered the potential impact of a vaccine when distributed through either proactive or reactive campaigns, with a hypothetical single-dose vaccine providing 90% protection against infection. We found that, in limited scenarios, the rare nature of spillovers means proactive vaccination would have a limited impact (0.21 deaths [95%h8CI: 0.08-0.43] averted per 10,000 doses over 30 years) and require 1.2 million doses. Reactive vaccination would also have a limited impact (0.27 deaths [95%CI: 0-2.75] averted per 10,000 doses over 30 years, 31,000 doses required, equivalent to 0.9 deaths [95%CI: 0-1] averted overall) due to the limited number of transmission generations. The use of a stockpile of 10,000 therapeutic mAb regimens that could prevent death in hospitalized patients could increase the impact to 49 deaths (95%CI: 23-87) averted over 30 years. Reactive campaigns were the most effective in livestock-amplified outbreaks (2.2 deaths [95%CI: 1.6-3] averted per 10,000 doses, 630,000 doses used in total) and extended outbreaks (467 deaths [95%CI: 293-463] averted per 10,000 doses, 690,000 doses used in total) but were highly dependent on delays to vaccine delivery. These findings suggest mAbs as the most impactful medical countermeasure under current epidemiology, with vaccines playing a significant role to limit the burden from NiV in livestock amplified and in theoretical extended outbreaks. However, the impact of both medical countermeasures will rely heavily on rapid distribution.

Evaluating the immunogenicity of clade 2 and clade 3 sarbecovirus spike protein nanoparticle vaccines in Syrian hamsters.

Halfmann PJ, Duffy A, Wang T … +2 more , Kawaoka Y, Kane RS

Vaccine · 2026 Jun · PMID 42114416 · Publisher ↗

The emergence of SARS-CoV-2 in human circulation in 2019 led to a push for universal coronavirus vaccine development. While many vaccine candidates against SARS-like viruses focus on close relatives of SARS-CoV-1 and SAR... The emergence of SARS-CoV-2 in human circulation in 2019 led to a push for universal coronavirus vaccine development. While many vaccine candidates against SARS-like viruses focus on close relatives of SARS-CoV-1 and SARS-CoV-2, more distant viruses in Sarbecovirus clades 2 and 3 have received less attention in vaccine studies. Here, we evaluate in hamsters the immunogenicity of nanoparticle vaccines displaying the spike proteins from clade 2 viruses Yunnan2011, YN2013, and HKU3-8 and from the clade 3 virus BtKY72. We find that our nanoparticle vaccines elicit pan-sarbecovirus reactivity in vaccinated hamster sera, although this binding is clade-biased. Hamster antisera from BtKY72 VLP-S vaccination potently neutralizes authentic SHC014 bat coronavirus, but both clade 2 and clade 3 antisera fail to neutralize authentic WIV1 bat coronavirus or the SARS-CoV-2 XBB variant. All vaccine groups provide limited but significant protection against a challenge with XBB virus.

Rational design and sequence optimization of an mRNA-LNP vaccine elicits protective immunity against infectious bronchitis virus in chickens.

Li R, Liukang C, Yang H … +5 more , Zhang X, Liang R, Zhao J, Zhang G, Zhao Y

Vaccine · 2026 Jun · PMID 42114415 · Publisher ↗

Infectious bronchitis virus (IBV) severely threatens the global poultry industry due to constant genetic variation and broad serotype diversity. Traditional live-attenuated vaccines often lack sufficient cross-protection... Infectious bronchitis virus (IBV) severely threatens the global poultry industry due to constant genetic variation and broad serotype diversity. Traditional live-attenuated vaccines often lack sufficient cross-protection and carry the risk of virulence reversion, necessitating safer alternatives. Here, we developed and evaluated a novel lipid nanoparticle-encapsulated mRNA (mRNA-LNP) vaccine against IBV. To maximize avian expression, we identified a chicken-derived Hsp70 5'-untranslated region that strongly drives translation. Using this backbone, we stabilized the spike (S) protein in its prefusion conformation by introducing diproline substitutions (2P) and mutating the furin cleavage site (FCSmut). We then optimized the mRNA secondary structure using the LinearDesign algorithm, which yielded superior in vitro translation efficiency and structural stability. Intramuscular vaccination of chickens rapidly elicited potent humoral and cellular immune responses, characterized by high-titer neutralizing antibodies and robust expansion of antigen-specific CD8 T cells. Following homologous challenge with a virulent IBV strain, the vaccine effectively alleviated clinical symptoms and reduced tracheal ciliary damage. It also drastically reduced viral replication in primary target organs and lowered respiratory viral shedding. Integrating avian-specific regulatory elements, conformational stabilization, and structural RNA optimization provides a highly effective framework for next-generation avian coronavirus vaccines.

Comparative immunogenicity of monomeric and tetrameric Nipah virus G glycoprotein-based vaccine candidates demonstrate robust antibody responses in both forms.

Mishra S, Kumar V, Kaur G … +10 more , Baby BA, Das A, Chatterjee A, Vishwakarma P, Sinha SK, Kumar A, Prasad VM, Dubey VD, Ahmed S, Samal S

Vaccine · 2026 Jun · PMID 42107904 · Publisher ↗

Nipah virus (NiV) is a highly pathogenic zoonotic virus with no licensed vaccine. The G surface glycoprotein of NiV plays a critical role in host cell attachment and is a prime vaccine target. In this study, we designed... Nipah virus (NiV) is a highly pathogenic zoonotic virus with no licensed vaccine. The G surface glycoprotein of NiV plays a critical role in host cell attachment and is a prime vaccine target. In this study, we designed and expressed two soluble recombinant variants of the G glycoprotein-monomeric and tetrameric forms-using a mammalian expression system to preserve the native-like structure. Both proteins were biochemically stable as measured up to one month at temperatures ranging from 2 to 8 °C and - 20 °C. While the monomer had a higher yield in transient expression, the tetramer more closely mimicked the native multimeric architecture and showed better biophysical stability. BALB/c mice immunized with either variant, along with AddaVax adjuvant, generated robust, long-lasting antibody and neutralizing responses persisting up to six months. Collectively, our findings demonstrate the robust immunogenicity of both soluble monomeric and tetrameric G immunogens, with the monomeric form offering high scalability, underscoring their suitability as subunit vaccine candidates against Nipah virus.

Multi-antigen transmission-blocking malaria vaccine elicits Th1-biased antibody responses and SMFA-confirmed oocyst reduction in Anopheles stephensi.

Pourhashem Z, Siasi S, Nourani L … +9 more , Yousefi H, Sani JJ, Vand-Rajabpour H, Raz A, Pirahmadi S, Zargar M, Djadid ND, Zakeri S, Mehrizi AA

Vaccine · 2026 Jun · PMID 42107903 · Publisher ↗

BACKGROUND: The persistent global burden of malaria highlights the urgent need for innovative vaccine strategies with the ability to block transmission of Plasmodium falciparum. This study presents a novel multi-componen... BACKGROUND: The persistent global burden of malaria highlights the urgent need for innovative vaccine strategies with the ability to block transmission of Plasmodium falciparum. This study presents a novel multi-component Transmission Blocking Vaccine (TBV) formulation, which integrates the antigens APN-1, CelTOS, and cd-HAP with the adjuvants CPG, MPL, and QS-21, with the aim of inducing broad immune responses targeting multiple parasite and mosquito stages. METHODS: Recombinant antigens were expressed in E. coli and formulated as single-antigen or triple-antigen vaccine formulations, with or without adjuvants. BALB/c mice were immunized, and sera were collected for antibody and cytokine profiling. Functional activity was measured by standard membrane feeding assay (SMFA) using P. falciparum NF54 gametocytes and Anopheles stephensi. RESULTS: The multi-component vaccine elicited robust high avidity IgG antibody responses against all three antigens without evidence of antigenic interference. Notably, it induced robust Th1-type cellular responses, characterized by increased IFN-γ and TNF production, which are critical for effective anti-parasitic immunity. Efficacy was further demonstrated through the Standard Membrane Feeding Assay (SMFA), which revealed that the induced antibodies substantially reduced oocyst load, a promising pathway for advancing malaria vaccine development. CONCLUSION: These findings underscore the potential of multi-component TBV vaccines to induce efficient transmission blocking immune responses without compromising individual antigen performance. The multicomponent TBV approach offers a practical framework for simultaneously targeting multiple stages of malaria transmission and supports further development of combination transmission-blocking vaccine strategies.

Impact of standing orders on vaccine uptake: A systematic review.

Ellingson MK, Sudarsanam V, Goddard K … +3 more , Tomar A, Nachman S, Brewer NT

Vaccine · 2026 Jun · PMID 42105399 · Publisher ↗

OBJECTIVE: We sought to evaluate the impact of standing orders on vaccine coverage in clinical settings. METHODS: Two reviewers independently screened and included studies that evaluated use of standing orders either alo... OBJECTIVE: We sought to evaluate the impact of standing orders on vaccine coverage in clinical settings. METHODS: Two reviewers independently screened and included studies that evaluated use of standing orders either alone or in combination with other interventions and collected data on vaccine coverage. We extracted effect sizes for studies that used only standing orders as an intervention and had a comparison group. RESULTS: The search yielded 56 eligible studies, 22 of which evaluated standing orders-only interventions. Standing orders increased vaccine uptake by a median of 13 percentage points (IQR 2-20 percentage points). Eight of these studies had a comparison group including 1 randomized trial; 5 were at low risk of bias. The overall findings were similar those for seasonal influenza vaccine (median increase of 12 percentage points; IQR, 6-24; 7 studies) and pneumococcal vaccines (14 percentage points; 2-20; 5 studies), the two most studied outcomes. Multi-component studies paired standing orders with interventions for providers frequently (34%-63% of studies), patients often (20%-49%), and systems least often (3%-14%). CONCLUSIONS: Standing orders show one of the largest effects among vaccine uptake interventions. Future research should focus on randomized trials, childhood vaccination, and behavioral aspects of implementation in healthcare systems.

Retooling a novel influenza B hemagglutinin to redirect neutralizing antibodies against B/Victoria strains.

Carlock MA, Ross TM

Vaccine · 2026 Jun · PMID 42105398 · Full text

Since the COVID-19 pandemic, only influenza B viruses (IBVs) from the Victoria (B/VIC) lineage have continued to circulate in humans. The hemagglutinin (HA) protein of these viruses has undergone substantial antigenic ev... Since the COVID-19 pandemic, only influenza B viruses (IBVs) from the Victoria (B/VIC) lineage have continued to circulate in humans. The hemagglutinin (HA) protein of these viruses has undergone substantial antigenic evolution, rendering antibodies elicited by older IBVs less effective at neutralization and protection. The computationally optimized broadly reactive antigen (COBRA) influenza B HA protein, BC2, elicits cross-lineage neutralizing antibodies against pre-COVID-19 IBVs. However, following the disappearance of the Yamagata (B/YAM) lineage, BC2 HA required updating to improve protection against contemporary B/VIC strains. To address this, a series of point mutations were introduced into BC2 HA to redirect antibody responses toward modern B/VIC-like viruses. This modified HA, named BC17, was evaluated in mice for immunogenicity and protective efficacy. Immune responses were compared with those elicited by BC2 HA and a representative wild-type B/VIC HA, B/CO/17. Mice vaccinated with BC17 HA exhibited significantly higher hemagglutination-inhibition (HAI) and neutralization titers against B/VIC viruses compared to mice vaccinated with BC2 HA or B/CO/17 HA. Consistent with these findings, BC17-vaccinated mice experienced significantly less weight loss than BC2-vaccinated mice following viral challenge. Overall, BC17 HA elicited broadly protective antibody responses against recently circulating B/VIC strains. The enhanced neutralization elicited by BC17 HA relative to BC2 HA was hypothesized to result primarily from amino acid changes within the 160-loop, a key antigenic region located at the membrane-distal tip of HA. Modern B/VIC viruses in the V1a.3 subclade contain a characteristic three-amino acid deletion in this loop that is absent in older strains. The design of the BC17 HA incorporated these deletions along with additional mutations. Restoration of these deleted residues in a BC17 mutant HA modestly reduced HAI titers but did not abrogate protection against viral challenge, indicating that the 160-loop contributes to, but does not solely determine, the enhanced antigenicity of BC17 HA.

Oral immunization with attenuated Salmonella enterica serovar Enteritidis expressing dual-toxin antigen induces protective immunity against avian necrotic enteritis.

Li W, Li YA, Liu X … +4 more , Xie H, Zhao J, Feng Y, Shi H

Vaccine · 2026 Jun · PMID 42105397 · Publisher ↗

Necrotizing enteritis (NE) is an important enteric disease threatening the poultry industry. Given the ban on antibiotic growth promoters, vaccination has become a safe and effective control strategy. Recombinant attenua... Necrotizing enteritis (NE) is an important enteric disease threatening the poultry industry. Given the ban on antibiotic growth promoters, vaccination has become a safe and effective control strategy. Recombinant attenuated Salmonella vaccine (RASV) administered orally can induce comprehensive immune responses to specific antigens, thus exhibiting great prospects for inducing protective immunity against NE. In this study, a dual-toxin (PlcC and NetB) antigen expression cassette was delivered by a new attenuated Salmonella enterica serovar Enteritidis (S. Enteritidis) vector rSC0169 to construct the candidate vaccine rSC0169(pS-PGN). rSC0169(pS-PGN) effectively colonized the host lymphatic system and induced robust mucosal, humoral, and cellular immune responses to PlcC and NetB. Moreover, rSC0169(pS-PGN) alleviated intestinal lesions, improved the intestinal villus height-to-crypt depth ratio, promoted tight junction protein expression, and reduced pro-inflammatory cytokine levels. Overall, this study provides a promising NE vaccine candidate that confers protection in an experimental challenge model and lays a theoretical foundation for the development of vaccine platforms against other intestinal pathogens.

A novel subunit vaccine based on glycoprotein H and glycoprotein L fusion against pseudorabies virus infection.

Yu X, Xie S, Luo Y … +5 more , Zheng J, Feng Z, Yang L, Qing R, Yu X

Vaccine · 2026 Jun · PMID 42105396 · Publisher ↗

Pseudorabies (PR) is a highly infectious disease caused by pseudorabies virus (PRV), which leads to significant economic losses. Vaccination remains the most effective method to control PRV infection. To develop an effic... Pseudorabies (PR) is a highly infectious disease caused by pseudorabies virus (PRV), which leads to significant economic losses. Vaccination remains the most effective method to control PRV infection. To develop an efficient DIVA (differentiation of infected from vaccinated animals) vaccine against PRV, this study expressed the envelope glycoprotein H (gH), glycoprotein L (gL), and a recombinant gH-gL fusion protein in a mammalian cell expression system and evaluated their protective efficacy in a mouse model. Immunization with gH, gL, or gH-gL induced high levels of specific antibodies capable of neutralizing PRV, and elicited a Th1/Th2-mediated immune response. Neutralizing antibody titers in the gH-gL group were significantly higher than those in the other groups. After a lethal challenge with 2 × 10TCID of the PRV variant XiangA strain, the survival rate of the gH-gL group was 100%, which was significantly higher than that of the gH (40%) and gL (50%) groups. Even under a higher challenge dose of 10TCID, the survival rate in the gH-gL group remained 100%, outperforming that of mice vaccinated with a commercial inactivated vaccine (50%). Furthermore, after challenge, viral loads in tissues of the gH-gL group were almost undetectable, and no obvious pathological changes were observed. Our results demonstrate that the gH-gL recombinant fusion protein is a promising vaccine candidate for preventing and controlling pseudorabies epidemics in China.

Safety of supervised hospital vaccination in children at risk of hypersensitivity: A 9-year study.

Donesana M, Marseglia A, Laterza L … +5 more , Caimmi SME, Odone A, Muzzi A, Marseglia GL, Licari A

Vaccine · 2026 Jun · PMID 42105395 · Publisher ↗

INTRODUCTION: Fear of allergic reactions is a frequent cause of vaccine hesitancy among families of children with allergic diseases. Vaccination in a supervised hospital setting is often recommended for children consider... INTRODUCTION: Fear of allergic reactions is a frequent cause of vaccine hesitancy among families of children with allergic diseases. Vaccination in a supervised hospital setting is often recommended for children considered at increased risk of hypersensitivity. However, real-world data on the safety and impact of this approach in pediatric populations remain limited. METHODS: We performed a retrospective, single-center study including children referred for vaccination under allergist supervision between July 2016 and May 2025. Vaccines were administered at full dose in a hospital setting, with predefined post-vaccination observation periods. Immediate and delayed adverse reactions were recorded using standardized criteria. Vaccination status and delays were assessed in relation to national age-appropriate immunization schedules. RESULTS: A total of 180 children received 368 vaccine doses. Mean age was 4.2 years, and 62.2% were male. The main reasons for referral were food allergy and previous adverse events following immunization. Thirty-one children (17.2%) had a history of anaphylaxis, predominantly food-related. No cases of anaphylaxis or severe systemic reactions occurred during supervised vaccination. Mild, self-limited reactions were observed in five children (2.8%), accounting for 1.4% of vaccination visits. At referral, many children had delayed or incomplete immunization schedules. At the time of review, non-compliance was 28.9% for mandatory vaccines and 47.2% when mandatory plus recommended vaccines were considered; the median delay between vaccine prescription and supervised administration was 115 days. CONCLUSION: Supervised hospital-based vaccination is safe in children perceived to be at risk of hypersensitivity reactions, including those with previous anaphylaxis. A structured, allergist-led approach combining individualized risk assessment, standard-dose administration, and appropriate observation may facilitate completion of delayed immunization schedules and may help address vaccine hesitancy in allergic pediatric populations.

Prevalence and correlates of COVID-19 vaccine uptake among sexual and gender minority adolescents in the southern United States.

Lambert D, Luisi N

Vaccine · 2026 Jun · PMID 42105394 · Publisher ↗

Although the COVID-19 pandemic disproportionately affected vulnerable and minoritized communities, vaccine uptake among these populations remains understudied. This study examined the prevalence and predictors of COVID-1... Although the COVID-19 pandemic disproportionately affected vulnerable and minoritized communities, vaccine uptake among these populations remains understudied. This study examined the prevalence and predictors of COVID-19 vaccination among LGBTQIA+ adolescents aged 13-17 in the southern U.S. From July 2021 to April 2022, LGBTQIA+ youth were recruited from eight southern states via social media ads. Overall, 76.6% of enrolled adolescents had received the COVID-19 vaccination. Among those who were not vaccinated, 74.4% reported at least some likeliness to be vaccinated in the next three months. Vaccination was more likely among youth who were employed or living with a physical disability or brain injury, and less likely among those reporting housing instability, homelessness, or household receipt of public assistance. Differences in vaccine uptake may reflect policies requiring proof of vaccination in workplaces and healthcare settings, and highlight potential barriers related to factors that disproportionately affect historically minoritized communities and adolescents.

HPV vaccine and age of sexual debut of adolescents: A nationwide cross-sectional study.

Theotonio Dos Santos LF, Gomes AM, Oliveira DA … +6 more , Mattos AJC, Ribeiro GA, Cruz SS, Sant'Anna VAR, Rizzo LV, Fonseca HAR

Vaccine · 2026 Jun · PMID 42105393 · Publisher ↗

BACKGROUND: Reports from the literature indicate parental concern that sexual education and HPV vaccine may encourage early initiation of sexual activity. In this context, the present study aims to evaluate possible asso... BACKGROUND: Reports from the literature indicate parental concern that sexual education and HPV vaccine may encourage early initiation of sexual activity. In this context, the present study aims to evaluate possible associations between sexual education, adherence to HPV (Human Papillomavirus) vaccination, and the initiation of sexual activity among Brazilian students. METHODS: This study is based on the analysis of data from the 2019 National Survey of School Health, involving 165,838 participants of both sexes, and representative of the Brazilian school population. Data on demographics, sexual education [guidance on sexually transmitted infections (STIs) and pregnancy prevention], HPV vaccine uptake, and age of sexual initiation were collected. Frequency analyses, logistic regression, and the survey-adjusted Wald test were employed. A significance level of p < 0.05 was adopted. RESULTS: Among individuals aged 13 to 15 years who received counseling regarding STIs or Pregnancy Prevention, HPV vaccination was more likely in both males (STI prevention: aOR 1.69, 95% CI 2.03-1.40, p < 0.001; pregnancy prevention: aOR 1.22, 95% CI 1.45-1.03, p = 0.021) and females (STI prevention: aOR 1.60, 95% CI 1.98-1.30, p < 0.001; pregnancy prevention: aOR 1.44, 95% CI 1.76-1.20, p < 0.001). The survey-adjusted Wald test indicated differences in the mean age of sexual initiation associated with both STI and pregnancy prevention counseling. In both cases, these interventions were associated with a slightly later sexual debut, with mean differences of approximately two months. CONCLUSION: Sexual education in the form of guidance on STIs and pregnancy prevention is associated with higher HPV vaccine uptake, although no causal relationship or chronological relation can be stated on a cross-sectional dataset. STI education, pregnancy prevention counseling, or HPV vaccine uptake showed no clinically relevant association with early or late initiation of sexual activity, as the magnitude of the differences in means is negligible.

Effect of a third COVID-19 vaccine dose on the incidence of Long COVID among adults who completed a primary vaccine series: a target trial emulation in a community-based cohort.

Shen Y, Shahn Z, Robertson MM … +3 more , Gebo K, Nash D, CHASING COVID Cohort Study Team

Vaccine · 2026 Jun · PMID 42102594 · Publisher ↗

BACKGROUND: Evidence on whether a third COVID-19 vaccine dose lowers long COVID risk is mixed. We estimated the effect of receiving ≥1 third dose versus completing only a primary series on 6- and 12-month long COVID inci... BACKGROUND: Evidence on whether a third COVID-19 vaccine dose lowers long COVID risk is mixed. We estimated the effect of receiving ≥1 third dose versus completing only a primary series on 6- and 12-month long COVID incidence using a target-trial emulation in a U.S. community cohort. METHODS: We analyzed the CHASING COVID Cohort, a prospective, community-based study of U.S. adults. Eligible participants were ≥ 18 years, had completed a two-dose primary series, had no prior long COVID, and had no SARS-CoV-2 infection in the 3 months before time zero. Strategies compared were: receive a third dose at time zero vs. not receive a third dose during follow-up. Long COVID was defined as ≥1 new symptom at or beyond 3 months post-infection with concurrent activity limitation, both absent in the prior year. Follow-up was 6 and 12 months. We used a per-protocol analog: participants were artificially censored upon deviating from their assigned strategy or lost-to-follow-up, with inverse-probability weights to address selection due to censoring and time-varying confounding. We fit weighted pooled logistic models to estimate weighted incidence, differences, and ratios at each horizon. RESULTS: Across 16 sequential trials (18,930 person-trials; 4044 unique individuals), 3321 person-trials received a third dose at time zero and 15,609 did not. At 6 months, weighted long COVID incidence was 0.9% (95% CI, 0.5%, 1.3%) with a third dose vs. 1.0% (0.8%, 1.1%) without (risk difference (RD), -0.1%; 95% CI, -0.5%, 0.4%; risk ratio (RR), 0.93; 95% CI, 0.54, 1.44). At 12 months, incidence was 4.9% (4.1%, 5.9%) with a third dose vs. 4.5% (4.1%, 4.8%) without (RD, 0.4%; 95% CI, -0.5%, 1.4%; RR, 1.09; 95% CI, 0.90, 1.33). CONCLUSION: In this community-based target-trial emulation, receiving a third COVID-19 vaccine dose did not meaningfully reduce 6- or 12-month long COVID incidence compared with completing only a primary series.

Emerging lipids-based adjuvant delivery technologies for vaccines.

Dhuri K, Ubhe A

Vaccine · 2026 Jun · PMID 42097105 · Publisher ↗

Historically infectious disease pandemics have caused health emergencies for humans as well as livestock on numerous occasions. In such situations and on a routine basis vaccination has emerged as an effective interventi... Historically infectious disease pandemics have caused health emergencies for humans as well as livestock on numerous occasions. In such situations and on a routine basis vaccination has emerged as an effective intervention for prevention and eradication of pathogenic infections. As the field of vaccine research has progressed, next generation vaccine platforms including protein subunits, recombinant proteins, nucleic acids (DNA, mRNA) and more have been discovered which rely on more complex adjuvants with capability to function as delivery carriers for the vaccine modalities helping achieve effective immune response, stability and safety. Lipids-based particulate systems are emerging, promising and flexible choices as adjuvant delivery systems because their makeup can be adjusted to suit the vaccine modality and the delivery needs. In this review open-source literature on development and evaluation of lipids-based delivery platforms which can also serve as vaccine adjuvants is studied. The survey reveals that the most lipids-based vaccine adjuvant delivery systems are particulate, such as emulsions, micro/nanoparticles, and liposomes facilitating the delivery of vaccine modalities to antigen-presenting cells (APCs) or other target cells enabling the nucleic acid translation and protein synthesis. This article is aimed at providing an overview of the lipids-based adjuvant delivery platforms with respect to the literature reports enlightening their applications in the field of vaccines which would serve as a reference for scientists undertaking vaccine product development.

Leaving no child behind? developing zero-dose and under-immunized child archetypes to improve vaccine uptake in Nigeria.

Isah A, Ugochukwu EJ, Mbachu CO … +4 more , Agu IC, Ekwueme CN, Uzochukwu BSC, Onwujekwe O

Vaccine · 2026 Jun · PMID 42097104 · Publisher ↗

BACKGROUND: Nigeria bears the highest burden of zero-dose and under-immunized children. This paper characterizes archetypes of zero-dose and under-immunized children in Nigeria through a stakeholder-engaged process, to i... BACKGROUND: Nigeria bears the highest burden of zero-dose and under-immunized children. This paper characterizes archetypes of zero-dose and under-immunized children in Nigeria through a stakeholder-engaged process, to inform policy and programmatic responses toward reaching the unreached. DESIGN AND METHODS: A qualitative approach was used, comprising a rapid literature review and a qualitative survey over a two-day multi-sector stakeholder co-creation workshop. The workshop involved immunization stakeholders from a variety of sectors. Participants worked in near-homogenous groups to explore four archetypes of exclusion identified from literature, guided by a structured template. Narrative synthesis of group reports was performed and problem definitions for each archetype were discussed and validated in plenary. RESULTS: Each archetype of zero-dose and under-immunized children were linked to broader determinants of health including poverty, education, geography and displacement. Children residing in hard-to-reach rural areas faced significant logistical barriers, difficult terrain and inadequate transportation options including long travel distances to reach health facilities. Urban poor children, while geographically closer to health centres, often encounter affordability issues, misinformation, and competing livelihood priorities of caregivers that hinder immunization uptake. For the conflict-affected, nomadic, and migrant children, frequent displacement, insecurity, and lack of stable healthcare access were reported as primary barriers. Culturally excluded children experience hesitancy due to religious or traditional beliefs, social stigma, and distrust of caregivers in modern medicine. CONCLUSIONS: There are hidden dimensions of immunization inequity that should be fully explored in solving the problem of zero dose and non-vaccination. Addressing underlying causes of non-vaccination requires strengthened collaboration across sectors.

mRNA COVID-19 vaccine safety in adults from the Canadian national vaccine safety network.

Muller MP, Soe P, Shulha HP … +13 more , Isenor JE, Valiquette L, Sadarangani M, Vanderkooi OG, Kellner JD, Top KA, De Serres G, McGeer A, Kiely M, Marty K, Irvine M, Bettinger JA, Canadian Immunization Research Network

Vaccine · 2026 Jun · PMID 42092317 · Publisher ↗

The Canadian National Vaccine Safety Network (CANVAS) conducted active vaccine safety surveillance during the two-dose primary COVID-19 mRNA vaccine rollout in Canadian adults and expanded on the findings of prior active... The Canadian National Vaccine Safety Network (CANVAS) conducted active vaccine safety surveillance during the two-dose primary COVID-19 mRNA vaccine rollout in Canadian adults and expanded on the findings of prior active safety surveillance studies by including an unvaccinated control group. In this cohort study, vaccinated and unvaccinated adults from 7 provinces and territories were recruited to complete emailed surveys one week after each vaccine dose (or at registration for unvaccinated controls). The primary outcome was a health event that resulted in missed work or school or required medical consultation. Multivariable regression models examined health events associated with the first and second doses of BNT162b2 (Pfizer) and mRNA-1273 (Moderna) vaccines. Surveys were completed by 567,781 and 301,717 individuals following dose one and dose two, and by 14,984 unvaccinated participants. In the multivariate analysis, health events within a week following vaccination were higher among vaccinated individuals compared to controls, with risk ratios (RR) ranging from 2.3 [95% Confidence Interval (C·I.) 2.1 to 2.6] for the first dose of BNT162b2 to 7 [95% C·I. 6.3 to 7.8] for the second consecutive dose of mRNA-1273. Common symptoms included fatigue/malaise, headache, fever and joint pain, and most were self-limited. Health events requiring an ED visit or hospitalization were significantly increased after the first dose of mRNA-1273 (RR 2.1 [95% C.I. 1.5 to 3.1]) or the second consecutive dose of mRNA-1273 (RR 2 [95% C.I. 1.3 to 2.9]). In summary, self-limited health events were more common in the week following vaccination with a first or second dose of an mRNA COVID-19 vaccine, compared with controls, with the highest frequency occurring after a second dose of mRNA-1273. Health events requiring an ED visit or hospitalization were more common in participants who received the mRNA-1273 vaccine, compared with controls. This difference was not observed for the BNT1262b2 vaccine.

The impact of unspecific viral adsorption on pharmaceutical container surfaces in vaccine process development.

Kress M, Heindl-Wruss J, Schlegl R … +1 more , Jungbauer A

Vaccine · 2026 Jun · PMID 42092316 · Publisher ↗

Unspecific adsorption of viral particles to container materials represents an under-recognized source of product loss in vaccine and viral gene-therapy manufacturing. While protein adsorption is well described, dedicated... Unspecific adsorption of viral particles to container materials represents an under-recognized source of product loss in vaccine and viral gene-therapy manufacturing. While protein adsorption is well described, dedicated investigations of viral particle adsorption remain limited. Understanding virus-surface interactions and selecting appropriate container materials is essential, as adsorption can cause substantial product losses, particularly during process steps involving purified viruses. These losses are further amplified by the low viral protein concentrations typically used in vaccine development, combined with high surface-to-volume ratios in small-scale operations, potentially compromising analytical accuracy, mass balance assessments, and subsequent decision-making. We evaluated viral particle adsorption across commonly used pharmaceutical containers, including PETG bottles and single-use bags, using multiple model viruses. All container types exhibited measurable nonspecific adsorption, enabling differentiation between low- and high-binding materials. Scanning electron microscopy and contact angle measurements identified distinct surface appearances and material-dependent differences in viral binding, with surface energy dominated by non-polar, hydrophobic interactions. These surface properties could be modulated through excipient addition. Excipient screening identified effective mitigation strategies, with surfactants such as Pluronic F-68 and proteins such as albumin nearly eliminating viral adsorption. These findings highlight the need to consider adsorption effects early in vaccine development and underscore the value of selecting low-binding materials and suitable excipients to safeguard process performance and product recovery.

Preparation and comparative evaluation of conjugate and whole-cell killed vaccine candidates against Salmonella enterica serovar Typhimurium.

Ahmad A, Yousaf Z, Naeem M … +10 more , Yasin M, Saleemi MK, Tahir MW, Raza QS, Afzal F, Karamat RS, Ambreen M, Sarwar Y, Iqbal M, Ali A

Vaccine · 2026 Jun · PMID 42090745 · Publisher ↗

Poultry is one of the largest and rapidly growing industries in Pakistan. Avian salmonellosis is among the most prevalent bacterial infections in poultry. A preventive vaccine in chicken is needed against food-borne zoon... Poultry is one of the largest and rapidly growing industries in Pakistan. Avian salmonellosis is among the most prevalent bacterial infections in poultry. A preventive vaccine in chicken is needed against food-borne zoonotic Salmonella enterica serovar Typhimurium. The surface polysaccharide-protein conjugate vaccine and whole-cell killed vaccine candidates were prepared against a poultry isolate of S. Typhimurium followed by immunogenicity evaluation in mice and protection studies in chicken. The O-specific polysaccharide (OSP) antigen of S. Typhimurium was directly conjugated to two carrier proteins: diphtheria toxoid (DT) and bovine serum albumin (BSA) using reductive amination chemistry whereas, whole-cell killed vaccine candidates were prepared using formalin and heat. Direct conjugation of S. Typhimurium OSP with DT and protection studies of the prepared conjugates in chicken have not been reported before. This enabled conjugate vaccine candidates to produce significantly (p < 0.05) better immunity in mice than the control group and comparable to that of killed vaccines, that presented a very high response. In chicken, the prepared vaccine candidates elicited adequate immunogenicity comparable to the available commercial live attenuated vaccine. The layers in vaccinated groups, specifically in conjugate vaccinated groups, were well protected against the given pathogenic challenge as compared to the unvaccinated birds which showed reduced growth and feed consumption, oviduct atrophy and decreased egg production in addition to other gross and histopathological lesions. The current study reports the first successful comparison of the S. Typhimurium OSP-Protein conjugate vaccine candidates with live and killed Salmonella vaccines in poultry.
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