Pulendran B. Systems vaccinology and the architecture of human immunity. Nature. 2026 Aug;656(8129):833-842.
doi: https://doi.org/10.1038/s41586-026-10753-8
Editorial comment: Systems vaccinology is redefining how we understand and design vaccines. By integrating multi-omics, computational biology, and increasingly artificial intelligence, it reveals how genetics, metabolism, the microbiome, and coordinated immune networks determine vaccine responses. The next challenge is translation: turning these insights into safer, more effective vaccines and integrating them into clinical development and regulatory practice.
Kulkarni PS, Potey AV, Gupta SK, Kodre A, Basu I, Shukla V, Barge V, Munshi R, Mishra AC, Vadakkedath R, Oldach D, Reddy PS, Yeolekar L, Poonawalla CS, Dhere RM, Arankalle VA, Kulkarni R, Gunale B; Dengue-mAb-02 Study Group. Safety and Preliminary Efficacy of Dengue Monoclonal Antibody in Adult Patients: A Randomized Clinical Trial. JAMA Netw Open. 2026 Aug 3;9(8):e2629979.
doi: https://doi.org/10.1001/jamanetworkopen.2026.29979
Editorial comment: A promising milestone in dengue therapeutics. In this Phase 2 randomized trial, a pan-serotype monoclonal antibody was safe and produced rapid reductions in viremia and fever, particularly at 5–7 mg/kg. As the first therapeutic against wild-type dengue to demonstrate preliminary efficacy in humans, these findings could represent an important step toward a specific treatment for dengue, although larger clinical trials are needed.
Wong JM, Acevedo PK, Whitehead S, Durbin A, DeSale H, Jones FK, Medina FA, Rovira-Diaz E, Prutzman K, Leao IC, Wang T, Desilva A, Harris E, Katzelnick L, Salje H, Weiskopf D, Adams LE, Paz-Bailey G. Dengue vaccines: The role of a correlate of protection in evaluating vaccine safety and risk. Vaccine. 2026 Aug 13;88:128599.
doi: https://doi.org/10.1016/j.vaccine.2026.128599
Editorial comment: Dengue continues to expand globally, yet vaccine development remains constrained by the absence of a validated correlate of protection (CoP). Establishing a reliable CoP could reduce dependence on large and costly Phase 3 efficacy trials, accelerate vaccine licensure, and facilitate evaluation across different populations. Experts have identified serotype-specific neutralizing antibodies as the most promising biomarker, particularly in DENV-naïve individuals, while emphasizing the urgent need for standardized assays and regulatory alignment. Advancing CoP validation could be a critical step toward faster and broader access to safe and effective dengue vaccines.
Kazi F, Shapland CY, Spiga F, Villanueva G, Cornish RP, Henschke N, Cogo E, Sebastianski M, Aarabi M, Bergman H, Buckley B, Clayton GL, French CE, Liu J, Madley-Dowd P, Pelone F, Petkovic J, Probyn K, Saulle R, Savović J, Wilson R, Beck CR, Higgins JPT. Implications for future pandemics from a living systematic review and critical evaluation of observational studies of the effectiveness of COVID-19 vaccination against the Omicron variant. Vaccine. 2026 Sep 17;90:128993.
doi: https://doi.org/10.1016/j.vaccine.2026.128993
Editorial comment: This WHO-commissioned systematic review, including 79 studies and more than 53 million individuals, reinforces that COVID-19 vaccination remained strongly protective against severe or critical disease during Omicron predominance, particularly with mRNA vaccines. However, the high risk of bias across much of the observational evidence highlights an important lesson for future pandemics: better standardized surveillance, integrated data systems, and robust study designs are essential to generate reliable real-world vaccine effectiveness evidence.
Moran MC, Burnett E, Groome MJ, Michael F, Breiman RF, Robinson AL, Iniguez V, Mujuru HA, Goldfarb DM, Lungayo CL, Mandomando I, Bonkoungou IJO, Anwari P, Contreras-Roldán I, Enweronu-Laryea C, N’Zue K, Nalunkuma C, Trang NV, Gheorghita S, Sahakyan G, Nazurdinov A, Latipov R, Uwimana J, Rey-Benito G, Weldegebriel G, Mwenda JM, Parashar UD, Tate JE; Multi-National Subpopulations Study to Evaluate Rotavirus Vaccines (MNSSTER-V) project working group. Rotavirus vaccine effectiveness against rotavirus and acute gastroenteritis mortality: an analysis of pooled case-control studies from the MNSSTER-V dataset. Lancet Child Adolesc Health. 2026 Oct;10(10):699-709.
doi: https://doi.org/10.1016/S2352-4642(26)00158-6
Editorial comment: Rotavirus remains a major cause of diarrhoeal deaths in children under five. In this multinational study across 22 countries, rotavirus vaccination showed 75.8% effectiveness against rotavirus-positive acute gastroenteritis mortality. These findings reinforce that improving timely vaccine delivery and coverage remains essential to reducing preventable childhood deaths worldwide.
Cuello MA, Gomez-Valenzuela F, Wichmann I, Olawaiye AB. Global feasibility of cervical cancer elimination: a multidimensional scenario-based modelling analysis across 175 countries. Lancet Glob Health. 2026 Sep;14(9):104008.
doi: https://doi.org/10.1016/j.langlo.2026.104008
Editorial comment: Cervical cancer elimination will require more than HPV vaccination alone. Modeling across 175 countries found that structural readiness—including education, health-system capacity, governance, and financing—was a stronger predictor of elimination than national income. Comprehensive strategies addressing these barriers alongside vaccination offer the greatest opportunity to achieve WHO elimination targets by 2050.
Venezia O, Kane H, Du G, Coughlan HD, Johanson TM, Wang H, Tilstam P, Kazer SW, Gunner G, Hoagland DA, Basavappa MG, Ravichandran K, Ada E, Zhakyp A, Kumar S, Duizer C, Searle O, Provido CG, Joannas L, Yang S, Healy LB, Wang Q, Capocchi J, Dhillon BS, Slavoff S, Shan L, Henao-Mejia J, Franklin RA, Chiu IM, Ordovas-Montanes J, Jeffrey KL, Lieberman J, Allan RS, Kagan JC, Wu H, Jackson R. Functional chimeric mRNAs encode proteins in mammalian immunity. Nature. 2026 Sep 2.
doi: https://doi.org/10.1038/s41586-026-10982-x
Editorial comment: his study reveals a previously underappreciated mechanism regulating inflammation and immunity: protein-coding chimeric mRNAs generated through trans-splicing between distant genes. In macrophages, inflammation promotes interchromosomal interactions that facilitate these transcript-fusion events. Remarkably, a newly identified GSDMD–TMEM106A fusion protein enhances inflammasome-driven pore formation and IL-1β release. In vivo, it appears to act as a double-edged sword—strengthening antibacterial defense while potentially worsening lethal sepsis. These findings uncover an additional layer of immune regulation and provide new insight into the delicate balance between effective host defense and harmful immunopathology.
Batool R, Wang R, Obeid H, Kollmann TR, Langley JM, Lavoie PM, Abu-Raya B. RSV Bivalent Prefusion F Protein Vaccine in Pregnancy and Protection Against RSV-Associated Illness in Infants: A Systematic Review and Meta-Analysis. JAMA Pediatr. 2026 Sep 8.
doi: https://doi.org/10.1001/jamapediatrics.2026.4074
Editorial comment: Real-world evidence strongly supports maternal RSVpreF vaccination for protecting infants against severe RSV disease. In this meta-analysis of seven studies involving more than 7,000 infants, vaccination during pregnancy was 82% effective against RSV-associated hospitalization through 3 months of age and 78% effective through 6 months when administered at least 14 days before delivery. These findings reinforce maternal RSV vaccination as an effective strategy for protecting infants during their most vulnerable first months of life.
Kapelus DJ, Olwagen CP, Izu A, Ranchod H, Mukendi CK, Mutsaerts EAML, Koen A, Jose L, Kwatra G, Faustini SE, Richter AG, Madhi SA. Immunogenicity up to age 5 years following a single-dose or two-dose infant primary series of 10-valent or 13-valent pneumococcal conjugate vaccine each followed by a booster dose in South Africa: extended follow-up of a single-centre, open-label, non-inferiority, randomised controlled trial. Lancet Child Adolesc Health. 2026 Sep 8:S2352-4642(26)00164-1.
doi: https://doi.org/10.1016/S2352-4642(26)00164-1
Editorial comment: This extended follow-up supports the durability of a reduced 1+1 PCV13 schedule. Whether the primary dose was given at 6 or 14 weeks, serotype-specific immunity remained non-inferior to the conventional 2+1 schedule through 5 years of age. In contrast, PCV10 1+1 schedules failed to maintain non-inferiority beyond age 3 years. These findings provide important evidence supporting PCV13 schedule simplification in countries with well-established pneumococcal vaccination programs, and high vaccination coverages, potentially reducing doses while maintaining long-term immunity.
Ionescu IG, Ouakki M, Breton O, Panicker G, Unger ER, Gilca V, Sauvageau C. Follow up immunogenicity of a mixed vaccination schedule with one dose of nonavalent and one dose of bivalent HPV vaccines 36 months post-vaccination among boys and girls. Vaccine. 2026 Sep 3;92:129107.
doi: https://doi.org/10.1016/j.vaccine.2026.129107
Editorial comment: This study provides encouraging evidence for the interchangeability of HPV vaccines in two-dose schedules. In boys and girls aged 9–10 years, mixed 9vHPV/2vHPV schedules maintained robust immune responses through 36 months, with 100% retaining antibodies against HPV16 and HPV18 and responses comparable to the homologous two-dose 9vHPV schedule. These findings support the potential flexibility of mixed HPV vaccination schedules, although clinical effectiveness and implementation data are still needed before broader policy decisions can be made.
Vázquez-Narváez JA, Avilés-Robles M, Espinosa-Sotero C, Martínez-Longoria CA, Moreno-Espinosa S, Reyes-Berlanga ML, Chacon-Cruz E. Advancing Chikungunya Prevention and Vaccination in Mexico: A Position Paper by the Immunization Committee of the Mexican Association of Pediatric Infectious Diseases. Vaccines. 2026; 14(9):756.
doi: https://doi.org/10.3390/vaccines14090756
Editorial comment: Chikungunya is an expanding global health threat, with the potential to cause persistent musculoskeletal disease and long-term disability well beyond the acute infection. Recent vaccine advances, including live-attenuated and VLP platforms, offer new opportunities for prevention. However, vaccination should be integrated with vector control, strengthened surveillance, and rapid outbreak detection. This position paper provides evidence-based recommendations to help guide future chikungunya vaccination and prevention policies in Mexico.
Lee W, Lee J, Lee SM, Kim EH. Intranasal Adenoviral Vector Vaccination Induces Durable Antibody and T Cell Responses in the Respiratory Tract. Vaccines. 2026; 14(9):793.
doi: https://doi.org/10.3390/vaccines14090793
Editorial comment: Intranasal vaccination could address a major limitation of current respiratory vaccines: limited mucosal immunity. In this mouse study, a single intranasal adenoviral-vector dose generated robust systemic and respiratory IgA and CD8 T-cell responses, including lung-resident T cells, sustained for up to four months. Although clinical studies are needed, these findings support intranasal adenoviral vectors as a promising strategy for achieving durable immunity directly at the respiratory mucosa—the portal of entry for many respiratory pathogens.
Janes H, Gao F, Buchbinder S, Wiysonge CS, Louis K, Napoleon B, Mfiki A, Mapp D, Gray G. A Population-Based HIV Vaccine Efficacy Trial Design: Statistical Framework and Design Considerations. Vaccines. 2026; 14(9):794.
doi: https://doi.org/10.3390/vaccines14090794
Editorial comment: As HIV vaccine development advances toward broadly neutralizing antibody–based strategies, future efficacy trials face a new challenge: evaluating vaccines ethically in an era of highly effective HIV prevention. This proposal outlines a population-based, randomized proof-of-concept design integrating external data, decentralized trial methods, and strong community partnerships. Importantly, it could simultaneously assess vaccine efficacy and validate neutralizing antibodies as an immune correlate of protection, helping pave the way toward future HIV vaccine licensure.
Thurau NM, Tometten I, Lübke N, Michels BE, Höfler D, Rosing F, Sehr P, Remke K, Timm J, Silling S, Waterboer T, Schramm D, Freitag N. Immunologic Response and Clinical Course After Off-label Nonavalent HPV Vaccination in Juvenile-onset Recurrent Respiratory Papillomatosis Patients. Pediatr Infect Dis J. 2026 Aug 26.
doi: https://doi.org/10.1097/INF.0000000000005381
Editorial comment: This small case series provides intriguing evidence for a potential therapeutic role of HPV vaccination in juvenile-onset recurrent respiratory papillomatosis (JoRRP). In two children, nonavalent HPV vaccination induced robust neutralizing antibody responses and was temporally associated with undetectable HPV DNA in the airways and clinical stabilization without new papilloma growth. Although larger studies are essential, these findings support further investigation of HPV vaccination as an adjunctive strategy for this challenging HPV-associated disease.
Ferreira CDN, Royer CA, Confortin C, Marques NFQ, Presibella MM, Freund AA, Campos KR, Sacchi CT, Abbud A, de Lima GB, de Morais CNL, da Silva VG, E Silva KMP, da Costa MMOM, Gonçalves S, Araújo SIR, Rovaris DB, Delatorre E, Ribeiro-Rodrigues R, Alves PA, Strottmann DM, Zanluca C, Duarte Dos Santos CN, Naveca FG, Wallau GDL, Alcantara DMC, Fernandez Grillo ZDC, Santos HGG, Bello G, Gräf T; DENV study group. Genomic epidemiology of dengue virus serotype 3 lineage 3III_B.3.2 in Brazil: insights into its spread and dengue severity amid co-circulation of multiple dengue serotypes. Lancet Reg Health Am. 2026 Jun 2;61:101521.
doi: https://doi.org/10.1016/j.lana.2026.101521
Editorial comment: The reemergence of DENV-3 in Brazil after more than a decade of limited circulation highlights the rapidly changing landscape of dengue in hyperendemic settings. Genomic surveillance identified at least 14 introductions of the emerging 3III_B.3.2 lineage during 2023–2024, followed by diversification into six regional clades. Importantly, compared with DENV-1, DENV-3 was associated with higher odds of severe dengue (adjusted OR 1.47–1.94), as was DENV-2 (OR 1.24–1.71). Although secondary infections may partly explain these associations, the findings reinforce the risks created by co-circulation of multiple serotypes and underscore the importance of sustained genomic and epidemiological surveillance to anticipate severe dengue epidemics.
Mhanna D, Salman B, El Hakim R, et al. Therapeutic melanoma vaccines: Platforms, neoantigen strategies, and emerging combination immunotherapies. Therapeutic Advances in Vaccines and Immunotherapy. 2026;14.
doi: https://doi.org/10.1177/25151355261488241
Editorial comment: Therapeutic melanoma vaccines are emerging as a promising frontier in personalized cancer immunotherapy. Advances in tumor genomics, mRNA and other vaccine platforms, together with AI-assisted neoantigen identification, are enabling vaccines tailored to individual tumors. Particularly promising is their combination with immune checkpoint inhibitors, which may enhance tumor-specific T-cell responses. While tumor heterogeneity, immune escape, biomarkers, and manufacturing remain important challenges, melanoma vaccines could become an increasingly important component of precision oncology.
Na H, Lee SM, Ahn SH, Lee HK, Lee J, Choi KC. T cell-mediated tumor suppression by a self-amplifying mRNA-based melanoma vaccine in a syngeneic mouse model. J Control Release. 2026 Aug 10;396:115040.
doi: https://doi.org/10.1016/j.jconrel.2026.115040
Editorial comment: Self-amplifying mRNA represents an exciting platform for therapeutic cancer vaccines. In a mouse melanoma model, a Melan-A–targeted saRNA vaccine formulated with lipid inorganic nanoparticles suppressed tumor growth and enhanced tumor-infiltrating cytotoxic T-cell responses. Preventive vaccination also delayed tumor progression and promoted antigen-specific and memory T-cell responses. Although still preclinical, these findings highlight the potential of saRNA technology to expand the emerging field of melanoma immunotherapy.
Xu Z, Li J, Zhang Z, Fan J, Liu X, Pan H, Mao S, Zhen Y, Wen X, Chang H, Chen W, Zhu M, Chen L, Zhao L, Liu L, Cao G, Jin B, Chen L, Zhang C, Wang Z, Wang W, Xu D, Zeng M. Dynamic epidemiological changes of hand, foot, and mouth disease and real-world effectiveness of EV-A71 vaccination: A case study in Shanghai (2009-2023). Hum Vaccin Immunother. 2026 Dec;22(1):2656515.
doi: https://doi.org/10.1080/21645515.2026.2656515
Editorial comment: The introduction of EV-A71 vaccination in China has substantially changed the epidemiology of hand-foot-mouth disease (HFMD). In Shanghai, vaccination was associated with a 56.7% reduction in incidence, 95.2% reduction in severe disease, and elimination of reported fatalities, while the two-dose schedule provided approximately 90% protection against EV-A71-associated disease. However, the subsequent shift toward non-EV-A71 serotypes, particularly CV-A6 and CV-A10, highlights the next challenge: developing multivalent vaccines capable of providing broader protection against HFMD.
Pungartnik PC, Parellada CI, Mayumi Usuda Prado Rocha D, Queijo RG, Bierrenbach AL, Orengo JC. Premature mortality and years of potential productive life lost due to HPV-attributable cancers in Brazil and Mexico: 2011 Versus 2023. Hum Vaccin Immunother. 2026 Dec 31;22(1):2728247.
doi: https://doi.org/10.1080/21645515.2026.2728247
Editorial comment: HPV-attributable cancers continue to impose a substantial and preventable burden of premature mortality in Brazil and Mexico. From 2011 to 2023, estimated HPV-attributable deaths increased from 6,515 to 9,533 in Brazil and from 4,303 to 4,997 in Mexico. In 2023 alone, these cancers accounted for 97,404 years of potential productive life lost in Brazil and 51,735 in Mexico, while cervical cancer remained the dominant contributor. These numbers reinforce the urgency of expanding HPV vaccination, screening, early diagnosis, and equitable treatment to accelerate the elimination of HPV-related cancers across Latin America.
Halbrook M, Merritt S, Hoff NA, Mukadi P, Kompany JP, Musene K, Beya M, Kalengi H, Tambu M, Kelly JD, Ball AH, To A, MacGill T, Orr R, Myers T, Woods CW, Nicholson BP, Wong TA, Hensley LE, Kindrachuk J, Lehrer AT, Mbala-Kingebeni P, Rimoin AW. Bundibugyo virus glycoprotein seroreactivity following recombinant vesicular stomatitis virus-Zaire Ebola virus glycoprotein vaccination in outbreak-affected populations of the Democratic Republic of the Congo: a longitudinal cohort study. Lancet. 2026 Sep 12;408(10559):1019-1028.
doi: https://doi.org/10.1016/S0140-6736(26)01608-9
Editorial comment: Although no licensed vaccine currently targets Bundibugyo virus (BDBV), encouraging evidence suggests that the rVSV-ZEBOV Ebola vaccine generates cross-reactive antibodies against BDBV. In two cohorts from the Democratic Republic of the Congo, antibody reactivity to both EBOV and BDBV remained above baseline for up to five years after vaccination. While the clinical significance of these cross-reactive antibodies remains uncertain, these findings support evaluating existing Ebola vaccines during BDBV outbreaks while BDBV-specific vaccines are developed.
Andraweera PH, Jeffs E, Wang B, Marshall HS. Preparing for Future Group B Streptococcus Vaccines: Perspectives of Pregnant Women in Australia. Vaccines. 2026; 14(9):807.
doi: https://doi.org/10.3390/vaccines14090807
Editorial comment: As maternal GBS vaccines approach potential implementation, understanding acceptance among pregnant women will be as important as demonstrating vaccine efficacy. In this Australian qualitative study of 31 pregnant women, infant wellbeing emerged as the strongest driver of vaccine acceptance, with participants generally preferring maternal vaccination over intrapartum antibiotic prophylaxis. However, concerns about vaccine safety and limited knowledge of GBS remained important barriers. The findings emphasize that successful maternal GBS vaccination programs will require more than vaccine availability: trusted healthcare providers, clear evidence-based communication, and accessible, flexible, woman-centered delivery strategies will be essential to translate a new vaccine into high uptake and meaningful protection for newborns.
Dudley MZ, Ali H, Villaescusa MR, Law B. Incidence, risk factors, and association with vaccination of thrombocytopenia and immune thrombocytopenia (ITP): A scoping review. Vaccine. 2026 Sep 3;92:129120.
doi: https://doi.org/10.1016/j.vaccine.2026.129120
Editorial comment: Thrombocytopenia is a rare event with multiple potential causes, making careful assessment essential when evaluating vaccine safety signals. This updated Brighton Collaboration review found background incidence estimates ranging widely from 1.6 to 92.1 cases per 100,000 person-years and identified numerous non-vaccine risk factors. Evidence consistently supports an increased risk of immune thrombocytopenia (ITP) following measles-containing vaccines, while several studies also identified increased risk after adenoviral COVID-19 vaccines. In contrast, most studies found no association with other vaccines, including mRNA and inactivated COVID-19 vaccines. These findings reinforce the importance of standardized case definitions and consideration of background risk when assessing adverse events following immunization.
Pickering A, Wise PH, Maldonado YB. Pediatric Vaccination and Pandemic Preparedness in Humanitarian Settings. Pediatr Clin North Am. 2026 Oct;73(5):953-964.
doi: https://doi.org/10.1016/j.pcl.2026.04.006
Editorial comment: Disease outbreaks are becoming more frequent and complex, with children in humanitarian and conflict-affected settings bearing a disproportionate burden. Millions of zero-dose children remain especially vulnerable to vaccine-preventable and emerging viral diseases. Protecting these populations requires more than vaccine availability: community engagement, effective infodemic management, resilient and integrated delivery systems, reliable surveillance, and context-adapted strategies are essential. Innovations such as mobile vaccination teams, novel financing, and stronger data coordination are promising but require further evidence. Lessons from COVID-19 reinforce the need for equitable, ethical, data-driven, and One Health-informed approaches that place children’s right to health at the center of pandemic preparedness and global health security.
Essink BJ, Vermeulen W, Andrade C, Mazur M, de Rooij R, Heijnen E, Casula D, Xing R, Tovar MP, Garner V, Albano FR. Immunogenicity and safety of an MF59-adjuvanted cell-derived higher-dose quadrivalent influenza vaccine (aQIVc) in adults aged 50 years or older: a phase 3 randomised controlled trial. Lancet Infect Dis. 2026 Sep 10:S1473-3099(26)00410-X.
doi: https://doi.org/10.1016/S1473-3099(26)00410-X
Editorial comment: This large phase 3 trial involving more than 7,600 adults aged ≥50 years evaluated a novel MF59-adjuvanted, cell-derived, higher-dose quadrivalent influenza vaccine (aQIVc). The vaccine produced superior immune responses compared with standard-dose adjuvanted egg-derived vaccine for all four influenza strains. Compared with recombinant high-dose-antigen vaccine, non-inferiority was demonstrated for A/H1N1 and both B strains, but not A/H3N2. Although aQIVc caused more local and systemic reactions, these were predominantly mild-to-moderate and transient, with no safety concerns identified. These findings support combining cell-based manufacturing, higher antigen content, and adjuvantation as a promising strategy to enhance influenza immunity in older adults.
Bastian, A.R., Menten, J., Tolboom, J. et al. Immune correlates of protection against RSV following Ad26.RSV.preF–RSV preF vaccination of adults aged >60 years. npj Vaccines. Aug 2026:
doi: https://doi.org/10.1038/s41541-026-01557-y
Editorial comment: Identifying reliable correlates of protection (CoPs) against RSV remains a major goal in vaccinology. In adults >60 years vaccinated with an investigational Ad26.RSV.preF–RSV preF vaccine, increases in both preF-specific IgG and RSV-neutralizing antibodies were significantly associated with reduced RSV-mediated acute respiratory infection and lower respiratory tract disease. Importantly, these findings were validated in a second phase 3 efficacy trial, strengthening the evidence for both markers as potential CoPs. Additional antibody profiling suggested that preF-specific IgG3 and IgG2 may also contribute to protection. Establishing validated RSV CoPs could become an important tool for evaluating and accelerating future RSV vaccine development.
