Background PT Bio Farma (Persero), an Indonesian state-owned pharmaceutical company, developed IndoVac, a recombinant protein subunit vaccine for active immunization against SARS-CoV-2. IndoVac is based on the RBD of the spike protein of the ancestral Wuhan-Hu-1 SARS-CoV-2 strain. Each 0.5-mL dose contains 25 μg of recombinant SARS-CoV-2 RBD protein, 750 μg of AlOH, 750 μg of CpG 1018 as an adjuvant, 2.226 mg of NaCl, and 0.923 mg of tris(hydroxymethyl)aminomethane. This phase 3 study evaluated the immunogenicity and safety of IndoVac in adolescents aged 12–17 years in West Sumatra Province, Indonesia, using Covovax as an active comparator. Methods We conducted an observer-blind, randomized, active-controlled trial. Participants with no previous COVID-19 vaccination received two doses of IndoVac or Covovax 28 days apart and were followed for 12 months after the second dose. The primary immunogenicity endpoint was the geometric mean ratio (GMR) of neutralizing antibodies against circulating Omicron variants at Day 14 after the second dose. Seropositivity, seroconversion, anti-RBD IgG responses, antibody persistence, and safety were assessed. Results A total of 649 participants were enrolled between 9 October and 22 November 2022, received at least one dose of the study vaccine. The GMR of neutralizing antibodies against the circulating Omicron variant at 14 days after the second dose was 1.18 (95% CI, 1.14–1.20), meeting the World Health Organization (WHO) non-inferiority criterion for immunobridging (95% CI lower bound >0.67). Neutralizing antibody levels were maintained for up to 12 months after the second dose. No serious adverse events (SAEs) were considered possibly, probably, or likely related to vaccination. Conclusions IndoVac was well tolerated and elicited a non-inferior neutralizing antibody response compared with Covovax. Despite being based on ancestral Wuhan-Hu-1 strain, IndoVac generated cross-reactive neutralizing responses against circulating Omicron variants, with humoral responses persisting for 12 months after the second dose.
Background Coxsackievirus B3 (CVB3) is an important pathogen associated with severe diseases such as myocarditis, pancreatitis, hepatitis, and hand, foot, and mouth disease (HFMD), yet no licensed CVB3 vaccine is available. Methods In this study, four clinically isolated CVB3 strains were characterized to identify a suitable vaccine candidate. KM50-W07, belonging to the predominant genotype E circulating in mainland China and exhibiting robust replication in Vero cells (7.75 Log10TCID₅₀/mL), was selected. Results An experimental inactivated vaccine based on KM50-W07 induced high neutralizing antibody titers (9.00–10.58 Log₂) in BALB/c mice and demonstrated broad cross-neutralization against multiple CVB3 genotypes (7.00–9.58 Log₂). Maternal antibodies from immunized female mice provided complete protection in neonatal mice against lethal CVB3 challenge. Conclusion The CVB3 vaccine candidate strain KM50-W07, with high growth titer, good immunogenicity, and genetic stability, was successfully screened, providing an experimental basis for developing inactivated CVB3 vaccines for global and especially Chinese prevention and control efforts.
Background Rotavirus is a principal etiological agent of severe acute gastroenteritis in young children, for which vaccination constitutes the cornerstone of prophylactic intervention. However, to our knowledge, few studies have comprehensively assessed the differential population impacts of alternative rotavirus vaccination strategies within China. This study was therefore conducted to quantify the effect of vaccination on the epidemiological dynamics of rotavirus-associated gastroenteritis in Shanghai. Methods An age-structured Susceptible-Infected-Recovered-Susceptible (SIRS-type) compartmental model incorporating the effects of vaccine interventions was developed. Epidemiological data on reported cases were sourced from the infectious disease surveillance system. Scenario-based simulations were employed to evaluate vaccine efficacy and the prospective outcomes of strategic adjustments to the vaccination program. Results The model demonstrated a high degree of fit with observed epidemiological data over the calibration period from July 2015 to April 2024 (R2 = 0.747, RMSE = 58.55 cases/month; LOO R2 = 0.423). The implementation of the RotaTeq vaccination program resulted in an estimated cumulative reduction of 20.0% (95% CI: 18.9–21.6%) in the whole population and 24.6% (95% CI: 23.0–26.5%) among children under 5 years, relative to a no-RotaTeq counterfactual. Simulations indicated that optimizing the vaccination schedule of the Lanzhou lamb rotavirus vaccine (LLR) and augmenting coverage rates are effective strategies for outbreak mitigation. The introduction of Lanzhou lamb reassortant rotavirus vaccine, live, oral, trivalent (LLR3) and oral hexavalent reassortant rotavirus vaccine (WH-HRV) would further reduce the disease burden across all age groups, potentially controlling the epidemic to a minimal endemic level post-2029. Conclusions The incidence of rotavirus-associated gastroenteritis in Shanghai exhibited a discernible downward trend between 2015 and 2024, a decline associated with substantial contribution from the introduction of the RotaTeq vaccine. The optimization of existing vaccination protocols, in conjunction with the deployment of novel vaccines, is anticipated to be crucial for achieving more comprehensive and sustained control of rotavirus transmission in Shanghai.
Dengue has become a global threat affecting millions of people annually and contributing to a significant mortality burden. Vaccination is the most effective approach to prevent this disease in dengue-endemic regions. A thorough understanding of viral growth kinetics is critical for designing a robust and scalable vaccine manufacturing process. The current study aimed to optimize the key growth parameters of four recombinant live attenuated dengue serotypes, including harvest schedule, temperature, Multiplicity of infection (MOI), and metabolite concentration. Growth kinetics data, followed by a scale-up study, established the feasibility of multiple harvests for all four serotypes within a defined production window, with the first harvest optimally occurring between Days 4 and 8. All serotypes demonstrated strong responsiveness to low MOIs and temperature shifts, resulting in 2- to 25-fold increases in titer within a reduced time frame. Furthermore, metabolite profiling revealed distinct glutamine and glucose consumption dynamics, highlighting its importance for optimizing infection media. Taken together, these findings provide valuable insights into dengue virus production and define critical parameters that can support future optimization studies and large-scale production.
Background Delays in vaccination with the first/second dose of measles-containing vaccine (MCV1, MCV2) increases risk of measles transmission. MCV2 was added to Ethiopia's routine immunization schedule in 2019, administered at age 15 months. We describe age at measles vaccination and characteristics associated with timely vaccination following MCV2 introduction. Methods A secondary analysis from a 2021 cross-sectional household survey of children aged 12–35 months in Oromia, Ethiopia was conducted. MCV vaccination status and age at vaccination were determined from the child's vaccination card. The cumulative card-confirmed vaccination coverage of MCV1 and MCV2 (among children 24–35 months) by age at vaccination was estimated. Among children who received MCV, vaccination timing was classified as early (MCV1: <9 months; MCV2: <15 months), timely (MCV1: 9 to <10 months; MCV2: 15 to <16 months), or delayed (MCV1: ≥10 months; MCV2: ≥16 months). Characteristics associated with timely MCV1 vaccination were analyzed using multivariate logistic regression, with urban/rural stratification. Results Overall, 651 children aged 12–35 months (MCV1) and a subset of 270 children aged 24–35 months (MCV2) were analyzed. Cumulative MCV1 coverage was 59.9% by age 9 months and 76.3% by age 12 months, and MCV2 was 33.0% by age 15 months and 44.8% by age 24 months. MCV coverage was generally higher in urban compared to rural areas. Among vaccinated children, the proportion receiving early, timely, and delayed doses was 30.1%, 44.5%, and 25.3% for MCV1, and 28.6%, 41.2%, and 30.3% for MCV2, respectively. Characteristics associated with timely MCV1 vaccination differed in urban and rural areas, but common themes included increased caregiver immunization awareness and service delivery aspects. Conclusions Although most children who received MCV1 were vaccinated by 12 months, many received delayed doses. MCV2 coverage was low, irrespective of vaccination timing. Findings highlight the importance of routine catch-up vaccination policies and guidance, and the need for tailored strategies in urban and rural settings to improve MCV coverage and timely vaccination.
Unlike most viral infections, influenza requires annual vaccination because ongoing antigenic drift continually alters circulating strains. Despite widespread yearly immunization, influenza vaccine effectiveness (VE) often remains below 50% during a given season. Distinct vaccine platforms elicit different immune responses that reflect their underlying mechanisms of action. Consequently, combining multiple platforms through heterologous prime–boost strategies may provide a promising approach to broaden and strengthen protective immunity against influenza viruses. This review examines both licensed and emerging influenza vaccine platforms with an emphasis on strategies designed to enhance the breadth and durability of immune protection. In particular, we discuss heterologous vaccination approaches that incorporate different vaccine platforms and routes of administration to optimize immune responses against influenza viruses.
Background Following the introduction of the single-dose HPV vaccine in Pakistan, a social media campaign was implemented to increase HPV vaccine uptake among caregivers of adolescent girls in Sindh province, evaluated using the Fogg Behavior Model (FBM). Methods A six-week behavioral insights–informed social media campaign, co-developed with government partners and local influencers, was implemented on Facebook and Instagram during the Gavi-supported HPV vaccine introduction in Pakistan. A quasi-experimental pre-test post-test panel study was conducted in seven urban districts, surveying the same caregivers (n = 1344) at baseline and six weeks later. Caregivers reported their motivation and ability to vaccinate their adolescent daughter, their media exposure, and vaccination status. Logistic regression models assessed associations between social media exposure, behavioral drivers, and vaccination uptake among caregivers whose daughters were unvaccinated at baseline. Results HPV vaccination increased from 30% at baseline to 51% at follow-up. Facebook and Instagram exposure was near-identical across treatment and control arms (78% versus 77%), undermining the geographic contrast. Individual-level analyses (n = 945) showed that caregivers exposed to HPV vaccine messages on social media had nearly three times the odds of vaccinating their daughters (aOR = 2.66, 95% CI 1.91–3.71). This association attenuated but remained large and significant after controlling for motivation and ability (aOR = 1.94, 95% CI 1.54–2.44), consistent with the association operating partly through these behavioral pathways and partly through a residual association not fully explained by them. Social media exposure was also independently associated with increases in perceived importance of vaccination, perceived ease of access, and knowledge of vaccination locations. Conclusion Individual-level panel analyses are consistent with campaign-associated behavior change operating through the behavioral pathways specified by the FBM — motivation and ability. These findings highlight the value of individual-level exposure measurement and behavioral monitoring in future vaccine communication evaluations.
Background Determinants of COVID-19 vaccine confidence have been widely studied among unvaccinated individuals, but less is known about factors shaping confidence among those already vaccinated. Methods We conducted an online survey (December 2021) among 3171 fully vaccinated French-speaking adults in Belgium. Vaccine confidence (1–9 scale) was analyzed using stepwise regression including health variables, fear of COVID-19, and personality traits. Results Higher confidence was associated with comorbidities, fear of COVID-19, conventionalism, and authoritarian submission. Lower confidence was associated with self-reported adverse events and conspiracy beliefs. Psychological and experiential factors showed stronger associations than health characteristics alone. Conclusions Vaccine confidence remains heterogeneous among vaccinated individuals and is shaped by both psychological traits and post-vaccination experiences. These findings suggest that vaccine confidence is not a static attitude but a dynamic construct that remains associated with individual beliefs, emotional responses, and post-vaccination experiences. Addressing safety concerns and fostering trust may be essential to sustain engagement in ongoing vaccination programs.
The aim of this study was to determine the difference in seroprotection between fully and partially vaccinated hill tribe and stateless children aged five years in northern Thailand along with the factors associated with the absence of anti-HBs in these children since vaccine implementation began in 1992. A case–control study was conducted to collect information from hill tribe and stateless individuals living in villages in Mae Fah Luang District, Chiang Rai Province. Children with no prior immunization, delayed immunization, or incomplete hepatitis B vaccination were included. Children who were completely vaccinated were included as controls. A questionnaire was distributed and 3 mL blood samples were collected for the qualitative and quantitative detection of hepatitis B biomarkers. Logistic regression was applied to detect factors associated with the absence of anti-HBs. A total of 188 cases and 188 controls were included in the study; 54% were male, and 54.3% belonged to the Akha group. The overall prevalence of anti-HBs was 59.3%; 63.3% of anti-HBs was detected in children with complete vaccination (with 2 children positive for anti-HBc). The difference is 55.3% to 63.3% for completed vaccination. Children whose birth weight was <2500 g (AOR = 3.52; 95% CI = 1.39–9.12), whose mother belonged to the Yao group (AOR = 16.90; 95% CI = 2.00–142.57), whose mother practiced Christianity (AOR = 2.30; 95% CI = 1.18–4.46), and whose father was aged 30–39 years (AOR = 2.20; 95% CI = 1.01–4.80) were more likely to exhibit an absence of anti-HBs. The hepatitis B vaccine-induced immune response rate among hill tribe and stateless children remains undesirable, and an effective assessment program is needed to monitor this issue.
Vaccinations remain a cornerstone of public health, effectively reducing the burden of infectious diseases, particularly in children. However, the increasing number of routine vaccine injections, especially in low- and middle-income countries (LMICs), has raised concerns among parents and healthcare providers, potentially impacting vaccine acceptance and adherence. This scoping review aims to investigate the number of injections administered across different age groups in LMICs, with a focus on Africa, South and South-East Asia. Data was sourced primarily from the World Health Organization immunization portal, alongside information on vaccines in development from various global health organizations. The study analyzed routine injectable vaccines by age group, examining national immunization schedules to estimate the number of injections and healthcare visits required and the distribution of injections and visits across different regions. The review highlights the complexity of vaccination practices in LMICs, where children receive numerous injections due to the inclusion of multiple vaccines in the Expanded Program on Immunization. The findings suggest that while vaccines are critical for preventing infectious disease, the high number of injections and visits may contribute to vaccine hesitancy, necessitating a reassessment of immunization strategies. For instance, as new vaccines are progressively introduced, the total number of injections administered to infants in particular could rise from the current 12 to between 18 and 26 injections. This review contributes to the ongoing discourse on optimising vaccine delivery, advocating for the adoption of needle-free technologies and combination vaccines to reduce the number of injections and visits to improve vaccine uptake.
Background Interruption of measles virus transmission requires sustained population immunity of ≥95%. This study assessed measles immunoglobulin G (IgG) seropositivity and antibody levels among measles IgM-negative children during the 2022–2024 measles outbreaks in Tanzania. Methods A total of 526 measles IgM-negative samples were analyzed using a quantitative measles IgG enzyme-linked immunosorbent assay. Seropositivity was defined as an IgG concentration ≥200 mIU/mL. Data were analyzed using STATA version 15. Results Overall measles IgG seropositivity rate was 82.7% (95% CI: 79.4–85.9). Seropositivity was similar among children who received two doses of measles-containing vaccine (MCV) (83.6%) and those who received one dose (82.1%). Seropositivity rates did not differ significantly across age groups (1–<2 years: 83.7%, 2–4 years: 83.8%, 5–9 years: 78.1%, and 10–14 years: 83.3%; p = 0.632). However, children who received two MCV doses had significantly higher geometric mean concentrations (GMCs) of measles IgG antibodies than those who received one dose (637.8 mIU/mL [95% CI: 582.6–698.4] vs. 538.4 mIU/mL [95% CI: 506.0–571.8]; p = 0.002). GMCs were higher among children vaccinated at 9 months than among those vaccinated later (616.0 mIU/mL [95% CI: 570.8–665.6] vs. 539.0 mIU/mL [95% CI: 503.4–577.2]; p = 0.008). Samples collected during the 2022 outbreak were independently associated with IgG seronegativity (aOR = 2.56, p = 0.002). Conclusion IgG seropositivity remained below the ≥95% herd immunity threshold, indicating persistent immunity gaps among measles IgM negative children investigated during measles outbreaks. Strengthening timely uptake of two MCV doses is essential to interrupt measles transmission.
This article outlines a regulatory pathway utilizing the Post-Approval Change Management Protocol (PACMP) to address the challenges associated with vaccine composition updates in Japan. Seasonal influenza vaccines and COVID-19 vaccines require annual composition updates—including strains for live attenuated vaccines, antigens for inactivated or recombinant vaccines, and sequences for mRNA vaccines—and regulatory procedures must be completed before each immunization season.In October 2025, the Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices Agency introduced the PACMP for vaccine composition updates. This platform-based option, which enables rational development by leveraging the same manufacturing and analytical methods, is suited to vaccines requiring recurrent vaccine composition updates. Under this pathway, marketing authorization holders (MAHs) and regulatory authorities predefine change plans and acceptance criteria, allowing a prior confirmation application (Step 1) before vaccine composition recommendation. When the predefined acceptance criteria are met, a subsequent notification (Step 2) allows approval in as few as 20 business days, improving predictability in both regulatory review and routine immunization timelines. The PACMP also presents considerations. If the data obtained under the protocol do not meet the predefined acceptance criteria, MAHs must revert to the conventional partial change application. Although PACMP application fees are higher, Step 1 is required only once when the same protocol remains applicable across seasons, reducing annual regulatory workload.In conclusion, the PACMP represents a predictable and transparent regulatory option for managing vaccine composition updates, while future challenges include expanding its applicability to additional vaccine modalities and combination vaccines.
Background Humoral immunity wanes following SARS-CoV-2 mRNA vaccination. However, frequent breakthrough infections following the emergence of the Omicron variant make it difficult to evaluate long-term antibody decline attributable solely to vaccination. This study addresses this gap by characterizing long-term antibody waning after booster vaccination in SARS-CoV-2-naïve individuals. Methods SARS-CoV-2 spike protein-specific IgG (S-IgG) titers in the Keio University Healthcare Worker Vaccination Cohort have been monitored since February 2021. Using serial measurements of stored serum samples, we identified SARS-CoV-2-naïve participants who had received at least three doses of mRNA vaccine and had not received any additional vaccination for ≥2 years. Absence of previous SARS-CoV-2 infection was confirmed by serial questionnaires and persistently negative nucleocapsid protein-specific IgG (N-IgG). Temporal waning of S-IgG after the final vaccination was modeled using one-compartment, two-compartment, and bi-exponential decay models. Predictive performance of the models was compared using the leave-one-out information criterion. Results 19 individuals (11 with three doses, 7 with four doses, and 1 with five doses) met the selection criteria. S-IgG waning after the final vaccination was best described by the two-compartment model, with an initial phase of relatively rapid decline followed by a second phase with a substantially smaller decay slope. Conclusions Long-term waning of S-IgG following mRNA booster vaccination is best characterized by a two-compartment model. These findings provide a framework for evaluating long-term binding antibody kinetics after booster vaccination and may facilitate the evaluation of current and future mRNA vaccines.
Background: Real-world COVID-19 risk and COVID-19 vaccine effectiveness (VE) data in children with obesity, as measured by body mass index (BMI), remain scarce. Our objectives were to study the association of BMI and incidence of COVID-19 and related hospitalization in children and evaluate the effectiveness of the mRNA COVID-19 vaccine (COMIRNATY, Pfizer-BioNTech) two-dose primary series and booster according to BMI. Methods: We conducted a population-based cohort study of children aged 5–11 years in Singapore, from 1st September 2021 until 15th August 2023, covering the delta and omicron wave periods, using data extracted from national databases. Children were categorized according to BMI: underweight (BMI <5th centile), acceptable weight and overweight (BMI > 90th centile). The main outcomes were incidence of COVID-19 and related hospitalization. Multivariable adjusted analysis was conducted to measure association of outcomes and BMI category. Vaccine effectiveness (VE) was calculated using incidence rate ratios. Results: A total of 255,477 children (48.7% male) were included in the study, with the following distribution: underweight, n = 17,612 (6.9%), acceptable weight, n = 211,819 (82.9%), and overweight, n = 26,046 (10.2%). Children who were overweight were more likely to be infected compared to children with acceptable weight during delta (OR 1.26, 95% confidence interval [CI] 1.18–1.34) and omicron periods (OR 1.20, 95% CI 1.17–1.23).Primary vaccination was effective against infection compared to unvaccinated (VE range 18–20%) and hospitalization (VE range 65–71%) in all 3 BMI categories. Booster dose improved slightly in children with overweight VE (VE 27%, 95% CI 10%–41%) but was not effective against hospitalization (VE 95% CI 0–58%). Compared to acceptable weight, cumulative COVID-19 incidence rate was higher in overweight regardless of vaccination throughout the study. Conclusions: Children who were overweight had increased risk of COVID-19 throughout the delta and omicron periods. While primary series vaccination and booster dose were effective against infection in children who were overweight, despite vaccination, their incidence rate remained higher compared to vaccinated children with acceptable weight.
Background Despite high reported routine vaccination coverage at 9 and 18 months, measles outbreaks occur every 3–5 years in Viet Nam, as in other low- and middle-income countries. However, measles seroepidemiology and risk factors for low seroprevalence among children remain unclear. Methods We conducted two cross-sectional studies on newborns and pediatric cases aged 1 month to 5 years using stored samples and information from a birth cohort study (July 2017–September 2018), and surveillance for childhood acute respiratory infections (September 2017–August 2022) in Nha Trang, respectively. We assessed age-specific measles seroprevalence by enzyme immunoassay for anti-measles IgG antibodies and the associations with their characteristics using logistic regression. Results Of 1008 newborns, seroprevalence was 83.7%. We found lower measles seroprevalence in cord blood from mothers aged ≤24 years, compared with those aged ≥35 years (adjusted OR [95% CI]: 0.11 [0.04–0.26]), and from mothers in suburban communes (0.67 [0.47–0.96]). Among 1547 pediatric cases, seroprevalence was 43.0%, 68.0%, and 77.9% for those aged 1≤9 months, 9≤18 months, and ≥ 18 months, respectively, with the lowest seroprevalence of 26.0% at 8 months. We found lower measles seroprevalence among cases aged <9 months and 9≤18 months (adjusted OR [95% CI]: 0.43 [0.27–0.69] and 0.62 [0.43–0.89], respectively, compared with those aged ≥18 months), those in households with ≥4 members (0.62 [0.42–0.91]), and those without measles vaccination history (0.35 [0.26–0.48]). Conclusions Risk-based interventions, particularly early measles vaccination, should be considered for protecting vulnerable children from measles.
Recent infections and transmissions of highly pathogenic avian influenza (HPAI) H5N1 clade 2.3.4.4b viruses in humans and animals pose a significant global public health threat. Vaccination is the most effective method for preventing and controlling human infections; however, it is unclear whether the World Health Organization (WHO) candidate vaccine viruses (CVVs) can induce cross-neutralizing antibodies against H5N1 strains currently circulating in the Republic of Korea. In this study, we evaluated sera from ferrets immunized with four WHO HPAI H5 CVVs (clade 1 and clade 2.3.4.4b) against HPAI H5N1 clade 2.3.4.4b viruses isolated from poultry and mammalian outbreaks in the Republic of Korea during 2023–2024. Hemagglutination inhibition and microneutralization assays showed that ferret antisera raised against the H5N1 clade 2.3.4.4b CVVs exhibited broad cross-neutralization against most Korean isolates. Among these, antiserum derived from the A/Ezo red fox/Hokkaido/1/2022 showed the strongest cross-activity. However, ferret antisera raised against the A/Vietnam/1194/2004-derived clade 1 CVV showed negligible neutralizing responses. These findings suggest that H5N1 clade 2.3.4.4b CVVs are effective vaccine candidates for inducing cross-neutralizing antibodies and could play a critical role in preparedness efforts against potential human infections in the Republic of Korea.
Malaria remains a significant public health challenge in Rwanda, disproportionately affecting pregnant women. Despite existing control measures like Insecticide-Treated Nets (ITNs), Indoor Residual Spraying (IRS), and Intermittent Screening and Treatment in Pregnancy (ISTP), malaria transmission persists due to factors such as insecticide resistance. The RTS,S/AS01 (Mosquirix™) malaria vaccine offers a potential solution, demonstrating efficacy in reducing clinical malaria in children in clinical trials. This study aims to evaluate the potential impact of integrating the RTS,S/AS01 vaccine into Rwanda's infants' health programs. This study utilized existing data on malaria prevalence, vaccine efficacy, and healthcare infrastructure in Rwanda. Findings from this study will provide evidence-based recommendations for policymakers regarding the vaccine's incorporation into national malaria control initiatives, contributing to the pursuit of sustainable malaria elimination in Rwanda.
Animal models play a crucial role in preclinical vaccine testing, with mice and hamsters commonly used. This study evaluated the immunogenicity of a novel live attenuated SARS-CoV-2 vaccine candidate, CDO-7N-1, which was administered subcutaneously to hamsters and macaques. Despite both species producing robust responses upon intranasal inoculation, the vaccine induced robust neutralizing antibody responses only in hamsters and failed to elicit a detectable immune response in macaques. This discrepancy highlights the importance of selecting appropriate animal models and optimizing vaccination routes for accurately predicting human vaccine efficacy, thereby guiding future vaccine development strategies.
