Anti-HPV seropositivity and GMTs 3-8 years after a dose of quadrivalent and one month after a dose of nonavalent HPV vaccine.

Anti-HPV seropositivity and GMTs 3-8 years after a dose of quadrivalent and one month after a dose of nonavalent HPV vaccine.

Source publication
Article
Full-text available
The objective of this study was to assess the persistence of antibodies after a single dose of quadrivalent HPV vaccine (4vHPV) and the effect of a dose of nonavalent HPV vaccine (9vHPV) given 3–8 years later. Such data might be of interest in the decision-making process regarding the 2-dose course completion in non-compliant vaccinees in jurisdict...

Contexts in source publication

Context 1
... participants were seropositive to the HPV types included in the 4vHPV administered 3 to 8 years earlier and 58% to 87% had antibodies to the five other HPV types included in the 9vHPV vaccine. GMTs were 6.1 AU/ml, 7.7 AU/ml, 20.1 IU/ml and 6.3 IU/ml for HPV6, HPV11, HPV16 and HPV18, respectively (Table 1). GMTs for the other five HPV types not included in the 4vHPV vaccine varied from 2.0 to 5.2 AU/ml in subjects seropositive for these HPV types and from 0.3 to 1.3 in those classified as seronegative ( Table 2). ...
Context 2
... month post-9vHPV vaccine administration, the 31 parti- cipants (100%) were seropositive to all nine HPV types with a 36.1 to 89.1-fold increase of GMTs. (Table 1). The post- 9vHPV vaccine GMTs to HPV31, HPV33, HPV45, HPV52 and HPV58 were slightly higher (all p > 0.05) in subjects seropositive pre-9vHPV dose administration, increasing 24.3-82.1-fold in those seropositive and 62.1-236.0-fold in those seronegative ( Table 2). ...

Similar publications

Article
Full-text available
The HPV vaccine has shown sustained efficacy and consistent stabilization of antibody levels, even after a single dose. We defined the HPV16-VLP antibody avidity patterns over 11 years among women who received one- or three doses of the bivalent HPV vaccine in the Costa Rica HPV Vaccine Trial. Absolute HPV16 avidity was lower in women who received...

Citations

... Ages were aggregated in the following ranges to match current HPV vaccine policy and in response to differential immunogenicity by age group: 9-14 and 15-26. Studies with reported data aggregated across our age groups (e.g., ages 10-18) were excluded, with one exception: Gilca 2019 [20], a key source of single and extended dose data, which reported aggregated results for ages [13][14][15][16][17][18]. As prior research shows that younger groups tend to have higher immunogenicity [21], these data were coded as 9-14 for a more conservative estimate of immune response in alternative schedules. ...
... In total, 23 studies were included in the present analysis; four contributed to extended interval data only [26][27][28][29], two to single dose data only [10,30], one study contributed to both [20], and 16 to comparator data only [17,19,21,22,[31][32][33][34][35][36][37][38][39][40][41][42]. ...
... Three studies reported quadrivalent vaccine extended dose data: Gilca 2019 (one month) [20], LaMontagne 2013 (one month and 72 months) [27], and Neuzil 2011 (36 months) [28]. Extended interval demonstrated non-inferiority in the quadrivalent vaccine for HPV 18 at all time points and for HPV 16 at 36 months and 72 months. ...
Article
Full-text available
Alternative dosing schedules for licensed human papilloma virus (HPV) vaccines, particularly single dose and extended intervals between doses (>12 months), are being considered to address vaccine shortages and improve operational flexibility. We searched PUBMED/MEDLINE for publications reporting immunogenicity data following administration of one of the licensed HPV vaccines (2vHPV, 4vHPV, and 9vHPV) to females aged 9–26 years. We conducted non-inferiority analyses comparing alternative to standard schedules using mixed effects meta-regression controlling for baseline HPV status and disaggregated by vaccine, subtype, time point, and age group (9–14 and 15–26 years). Non-inferiority was defined as the lower bound of the 95% confidence interval (CI) for the geometric mean titer (GMT) ratio being greater than 0.5. Our search returned 2464 studies, of which 23 were included in data analyses. When evaluated against standard schedules, although robust immunogenicity was demonstrated across all multi-dose groups, non-inferiority of extended interval dosing was mixed across vaccines, subtypes, and time points. Single dose did not meet the criteria for non-inferiority in any comparisons. Sparse data limited the number of possible comparisons, and further research is warranted.
... VLP-based HPV vaccines have recently been shown to prevent cases of cervical intraepithelial neoplasias, with protection levels lasting for at least 10 years [19,20]. Moreover, recent studies show that a single dose of the HPV VLP-based vaccine can lead to long-lasting protection from HPV infection [21]. These vaccines are based on VLPs derived from over-expression of the capsid proteins in yeast (Gardasil vaccines) or in insect cells (Cervarix vaccine). ...
... Although aforementioned preclinical protective studies look promising, there are still some questions that remain to be answered with both candidate vaccines. For example, we still do not know if immune responses elicited by HPV16 L1-16L2 (aa 17-31) VLPs or mixed MS2-L2 VLPs will last 3-8 years, as has been shown with a single dose of Gardasil-4 [21]. Recent preclinical studies with four doses (25-50 µg/dose) of HPV16 L1-16L2 (aa 17-31) VLPs show that the antibodies are protective 1 year after immunization [69]. ...
Article
Full-text available
Human papillomaviruses (HPVs) are the most common sexually transmitted infections worldwide. Ninety percent of infected individuals clear the infection within two years; however, in the remaining 10% of infected individuals, the infection(s) persists and ultimately leads to cancers (anogenital cancers and head and neck cancers) and genital warts. Fortunately, three prophylactic vaccines have been approved to protect against HPV infections. The most recent HPV vaccine, Gardasil-9 (a nonavalent vaccine), protects against seven HPV types associated with ~90% of cervical cancer and against two HPV types associated with ~90% genital warts with little cross-protection against non-vaccine HPV types. The current vaccines are based on virus-like particles (VLPs) derived from the major capsid protein, L1. The L1 protein is not conserved among HPV types. The minor capsid protein, L2, on the other hand, is highly conserved among HPV types and has been an alternative target antigen, for over two decades, to develop a broadly protective HPV vaccine. The L2 protein, unlike the L1, cannot form VLPs and as such, it is less immunogenic. This review summarizes current studies aimed at developing HPV L2 vaccines by multivalently displaying L2 peptides on VLPs derived from bacteriophages and eukaryotic viruses. Recent data show that a monovalent HPV L1 VLP as well as bivalent MS2 VLPs displaying HPV L2 peptides (representing amino acids 17–36 and/or consensus amino acids 69–86) elicit robust broadly protective antibodies against diverse HPV types (6/11/16/18/26/31/33/34/35/39/43/44/45/51/52/53/56/58/59/66/68/73) associated with cancers and genital warts. Thus, VLP-based L2 vaccines look promising and may be favorable, in the near future, over current L1-based HPV vaccines and should be explored further.
... However, in both studies, the percentage of girls who were seropositive for vaccine-type HPV antibodies was high across all vaccinated arms, regardless of the number of doses received. In a subsequent Canadian study of girls aged 13-18 years, all were HPV16/18 seropositive following a single dose of Gardasil Ò provided through the national vaccination program three to eight years previously [38]. These immunogenicity studies are informative but affected by many of the same limitations as the national programme-based efficacy studies included in the previous systematic review by Markowitz et al. [17]. ...
Article
Full-text available
Objectives: This study aimed to systematically review the literature on the efficacy and immunogenicity of single-dose HPV vaccination compared to no vaccination or multi-dose schedules among vaccine trial participants. Methods: Medline, EMBASE, Global Health Database and Cochrane Central Register of Controlled Trials were searched for publications and conference abstracts (dated January 1999-August 2018) using MeSH and non-MeSH terms for human papillomavirus AND vaccines AND (immunogenicity OR efficacy/effectiveness) AND dosage. Search results were screened against pre-specified eligibility criteria. Data were extracted from included articles, and a narrative synthesis conducted on efficacy against HPV16/18 infection and humoral immunogenicity. Results: Seven of 6,523 unique records identified were included in the review. Six were nested observational studies of participants randomised to receive two or three doses in three large HPV vaccine trials, in which some participants did not complete their allocated schedules. One small pilot study prospectively allocated participants to receive one or no vaccine dose. Frequency of HPV16/18 infection was low (e.g. <1% for 12-month-persistent infection) in all vaccinated participants up to seven years post vaccination and did not significantly differ by number of doses (p > 0.05 in all cases). Frequency of infection was significantly lower in one-dose recipients compared to unvaccinated controls (p < 0.01 for all infection endpoints in each study). HPV16/18 seropositivity rates were high in all HPV vaccine recipients (100% in three of four studies reporting this endpoint), though antibody levels were lower with one compared to two or three doses. Conclusions: This review supports the premise that one HPV vaccine dose may be as effective in preventing HPV infection as multi-dose schedules in healthy young women. However, it also highlights the paucity of available evidence from purpose-designed, prospectively-randomised trials. Results from ongoing clinical trials assessing the efficacy and immunogenicity of single-dose HPV vaccination compared to currently-recommended schedules are awaited.
... The bivalent (2vHPV: contains AS04 adjuvanted HPV 16 and 18 virus like particles (VLPs)) and the quadrivalent (4vHPV: contains AAHS adjuvanted HPV 6,11,16,18 VLPs) HPV vaccines have been successfully used in immunization programs in different jurisdictions for over a decade. 1 Both vaccines induce immunity to HPV 16 and 18. These two high risk (carcinogenic) types are responsible for ≥70% of cervical cancers and a great majority (≥85%) of other HPV related cancers. ...
... Although these antibody titers were relatively low, they increased significantly after the administration of a dose of 9vHPV. 15,16 It is unclear if this increase in antibody titers was a prime or a booster response given the paucity of data regarding the magnitude of the immune response after a single dose of 9vHPV vaccine. ...
... The results from two clinical trials conducted in the same region (Québec City, Canada), by the same research team, in comparable populations, recruited during the same years (2015-2017) were included in this analysis. 15,16 In study A (NCT02567955), a dose of 9vHPV was administered 6 months after a single dose of 2vHPV (n = 86) as well as to naïve subjects (n = 88). In this study, [9][10] year-old subjects were recruited by invitation letters sent through schools to parents. ...
Article
The main objective of this post hoc analysis is to compare the magnitude of the immune response to HPV31/33/45/52 and 58 after a dose of 9vHPV vaccine given to naïve (previously unvaccinated) subjects and subjects previously vaccinated with a dose of 2vHPV or 4vHPV vaccine. Results from two clinical trials conducted in the same region, in comparable populations and by the same research team were included in this analysis. In study A, a dose of 9vHPV was administered 6 months after a single dose of 2vHPV as well as to naïve subjects. In study B, a dose of 9vHPV was administered 36-96 months (mean 65 months) after a single dose of 4vHPV. Blood samples were collected just before and one month post-9vHPV vaccine administration. For both studies, antibody responses were measured using the same 9-plex virus-like particle based IgG ELISA (M9ELISA). One month after 9vHPV dose administration, all subjects were seropositive to HPV 31/33/45/52 and 58. Subjects who had previously received 2vHPV or 4vHPV had significantly higher (1.8-8.0-fold) GMTs than naive subjects for HPV31/33/45/52 types but not for HPV58. GMTs to HPV31/33/45/52 and 58 were not significantly different between subjects who received a 2vHPV or 4vHPV dose prior to 9vHPV. The strong anamnestic response to one dose of 9vHPV given as late as 3-8 years after a single dose of 2vHPV or 4vHPV vaccine indicates these vaccines induced priming to types only included in the 9vHPV vaccine.
... 26 The relative titers across types are the same for the 9-10 year old pre-adolescents not yet sexually active and 13-18-years-old adolescents, an age group in which we cannot rule out sexual activity. 27,28 This observation suggests that adolescents vaccinated with one dose of vaccine are not getting significant boosting from viruses shed by their sex partners. A study conducted in the same province five years post vaccination program implementation showed a 1% combined prevalence of HPV6/11/16/18 DNA in [17][18][19] year-old sexually active girls. ...
... 6,29 Methods Data were obtained from two previously reported clinical trials conducted by our team, in Quebec City, Quebec, Canada. 27,28 The serological assays for both studies were performed using a 9-plex VLP IgG ELISA (M9ELISA) at the Centers for Disease Control and Prevention (CDC, Atlanta, USA). 30 Antibody titers were measured in International Units (IU/ml) for HPV16 and 18. ...
... The immunization status pre-second dose was assessed using regional vaccination registry data, reviewing individual vaccination cards, and confirming receipt of only single dose with the subjects and their parents. The pre-second dose blood samples included in this analysis were collected 1 or 6 months following the first dose in study A, 28 and 3-8 y after the first dose in study B. 27 In both studies, the post second-dose blood sample was collected after 1 month (range 21-41 d) ( Table 2). ...
Article
The objective of this analysis was to compare the anti-HPV GMTs and their distribution after a 6- month or a 3-8 year interval between two HPV vaccine doses. The results from two clinical trials, conducted by the same team in the same region, with serological assays performed at the same laboratory using the same ELISA methodology were compared. In the first study, 173 9-10 year-old girls and boys received two doses of 9vHPV vaccine at a 6-month interval; in the second study, 31 girls vaccinated with one dose of 4vHPV at the age of 9-14 years received a dose of 9vHPV 3-8 years later (mean 5.4 years). In both studies blood samples were collected before and 1 month post-second dose. Despite large differences in the time since the first dose, all subjects (100%) were seropositive to the common 4 HPV types (6, 11, 16 and 18) to both vaccines, with comparable GMTs and titer distributions before the second dose. One-month post-second dose, the GMTs increased 40- to 91-fold for those with a 6-month interval between doses and 60- to 82-fold for those with a 3-8 year interval. Titer distributions after the booster dose were comparable in the two studies. These results indicate that 2-dose HPV vaccination schedules with an interval of several years could be used for pre-adolescents. Intervals longer than 6 months may facilitate logistics for immunization programs and could be useful during periods of vaccine shortage or as a transition while the effectiveness of a one-dose schedule is being evaluated. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or of the Quebec Public Health Institute.