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Vaccine Oct 2023Individuals with human papillomavirus (HPV)-related disease remain at risk for subsequent HPV infection and related disease after treatment of specific lesions.... (Review)
Review
Individuals with human papillomavirus (HPV)-related disease remain at risk for subsequent HPV infection and related disease after treatment of specific lesions. Prophylactic HPV vaccines have shown benefits in preventing subsequent HPV-related disease when administered before or soon after treatment. Based on our understanding of the HPV life cycle and vaccine mechanism of action, prophylactic HPV vaccination is not expected to clear active persistent HPV infection or unresected HPV-associated dysplastic tissue remaining after surgery. However, vaccination may reasonably be expected to prevent new HPV infections caused by a different HPV type as well as re-infection with the same HPV type, whether from a new exposure to an infected partner or through autoinoculation from an adjacent or distant productively infected site. In this review, we describe the evidence for using prophylactic HPV vaccines in patients with HPV-associated disease before, during, or after treatment and discuss potential mechanisms by which individuals with HPV-associated disease may or may not benefit from prophylactic vaccines. We also consider how precise terminology relating to the use of prophylactic vaccines in this population is critical to avoid the incorrect implication that prophylactic vaccines have direct therapeutic potential, which would be counter to the vaccine's mechanism of action, as well as considered off-label. In other words, the observed effects occur through the known mechanism of action of prophylactic HPV vaccines, namely by preventing virus of the same or a different HPV type from infecting the patient after the procedure.
Topics: Female; Humans; Papillomavirus Vaccines; Papillomavirus Infections; Uterine Cervical Neoplasms; Human Papillomavirus Viruses; Vaccination
PubMed: 37704498
DOI: 10.1016/j.vaccine.2023.08.047 -
The Lancet. Global Health Feb 2024About half of the world's population lives in dengue-endemic areas. We aimed to evaluate the long-term efficacy and safety of two doses of the tetravalent dengue vaccine... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
About half of the world's population lives in dengue-endemic areas. We aimed to evaluate the long-term efficacy and safety of two doses of the tetravalent dengue vaccine TAK-003 in preventing symptomatic dengue disease of any severity and due to any dengue virus (DENV) serotypes in children and adolescents.
METHODS
In this ongoing double-blind, randomised, placebo-controlled trial, we enrolled healthy participants aged 4-16 years at 26 medical and research centres across eight dengue-endemic countries (Brazil, Colombia, Dominican Republic, Nicaragua, Panama, Philippines, Sri Lanka, and Thailand). The main exclusion criteria were febrile illness (body temperature ≥38°C) at the time of randomisation, hypersensitivity or allergy to any of the vaccine components, pregnancy or breastfeeding, serious chronic or progressive disease, impaired or altered immune function, and previous receipt of a dengue vaccine. Participants were randomly assigned 2:1 (stratified by age and region) using an interactive web response system and dynamic block assignment to receive two subcutaneous doses of TAK-003 or placebo 3 months apart. Investigators, participants, and their parents or legal guardians were blinded to group assignments. Active febrile illness surveillance and RT-PCR testing of febrile illness episodes were performed for identification of virologically confirmed dengue. Efficacy outcomes were assessed in the safety analysis set (all randomly assigned participants who received ≥1 dose) and the per protocol set (all participants who had no major protocol violations), and included cumulative vaccine efficacy from first vaccination to approximately 4·5 years after the second vaccination. Serious adverse events were monitored throughout. This study is registered with ClinicalTrials.gov, NCT02747927.
FINDINGS
Between Sept 7, 2016, and March 31, 2017, 20 099 participants were randomly assigned (TAK-003, n=13 401; placebo, n=6698). 20 071 participants (10 142 [50·5%] males; 9929 [49·5%] females; safety set) received TAK-003 or placebo, with 18 257 (91·0%) completing approximately 4·5 years of follow-up after the second vaccination (TAK-003, 12 177/13 380; placebo, 6080/6687). Overall, 1007 (placebo: 560; TAK-003: 447) of 27 684 febrile illnesses reported were virologically confirmed dengue, with 188 cases (placebo: 142; TAK-003: 46) requiring hospitalisation. Cumulative vaccine efficacy was 61·2% (95% CI 56·0-65·8) against virologically confirmed dengue and 84·1% (77·8-88·6) against hospitalised virologically confirmed dengue; corresponding efficacies were 53·5% (41·6-62·9) and 79·3% (63·5-88·2) in baseline seronegative participants (safety set). In an exploratory analysis, vaccine efficacy was shown against all four serotypes in baseline seropositive participants. In baseline seronegative participants, vaccine efficacy was shown against DENV-1 and DENV-2 but was not observed against DENV-3 and low incidence precluded evaluation against DENV-4. During part 3 of the trial (approximately 22-57 months after the first vaccination), serious adverse events were reported for 664 (5·0%) of 13 380 TAK-003 recipients and 396 (5·9%) of 6687 placebo recipients; 17 deaths (6 in the placebo group and 11 in the TAK-003 group) were reported, none were considered study-vaccine related.
INTERPRETATION
TAK-003 demonstrated long-term efficacy and safety against all four DENV serotypes in previously exposed individuals and against DENV-1 and DENV-2 in dengue-naive individuals.
FUNDING
Takeda Vaccines.
TRANSLATIONS
For the Portuguese, Spanish translations and plain language summary of the abstract see Supplementary Materials section.
Topics: Adolescent; Child; Female; Humans; Male; Dengue; Dengue Vaccines; Dengue Virus; Double-Blind Method; Hypersensitivity; Vaccination; Child, Preschool
PubMed: 38245116
DOI: 10.1016/S2214-109X(23)00522-3 -
Vaccine Nov 2023We conducted a trial to demonstrate immunogenic equivalence of three consecutive manufacturing lots of Takeda's tetravalent dengue vaccine candidate, TAK-003, and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
We conducted a trial to demonstrate immunogenic equivalence of three consecutive manufacturing lots of Takeda's tetravalent dengue vaccine candidate, TAK-003, and further assessed its safety and reactogenicity.
METHODS
Healthy US adults (n = 923) randomized 2:2:2:1 to four groups received two doses of one of three TAK-003 lots or placebo on Days 0 and 90, with follow-up to Day 270. Primary endpoint evaluated lot-to-lot equivalence of geometric mean neutralizing titers at Day 120 against each of 4 dengue serotypes in baseline seronegative participants. Solicited local and systemic, and unsolicited adverse events (AEs) were assessed for 7, 14 and 28 days after each dose, respectively. Serious AEs (SAE) were monitored throughout the study.
RESULTS
Eight of 12 prespecified equivalence comparisons were met in the per-protocol set but failed marginally in the other 4 mainly due to loss of statistical power following higher than anticipated baseline seropositivity and drop-out rates. All three TAK-003 lots elicited high rates of tetravalent dengue seropositivity (96.7 %, 93.0 % and 97.5 % at Day 120; 91.0 %, 80.5 % and 85.7 % at Day 270) and had similar reactogenicity profiles with no vaccine-related SAEs.
CONCLUSIONS
The three lots of TAK-003 were immunogenic for all four dengue serotypes and well tolerated in healthy adults. Despite not meeting all equivalence comparisons, no major differences were observed between lots and the data support acceptable consistency of the manufacturing process. Trial registrationClinicalTrials.gov identifier: NCT03423173.
Topics: Humans; Adult; Dengue; Dengue Vaccines; Vaccines, Combined; Vaccination; Double-Blind Method; Immunogenicity, Vaccine; Antibodies, Viral; Antibodies, Neutralizing
PubMed: 37884415
DOI: 10.1016/j.vaccine.2023.09.049