Skip to main content

Table 1 Summary of vaccine immunogenicity and efficacy studies conducted in low and middle income countries

From: Vaccines against human papillomavirus in low and middle income countries: a review of safety, immunogenicity and efficacy

Study Study population Study vaccine Study design Vaccination schedule Follow-up Serological assays/HPV DNA assay Study end points Main results
Perez et al. (2008) [15] A total of 6004 healthy female subjects aged 9–24 were recruited from Brazil, Mexico, Colombia, Costa Rica, Guatemala and Peru Quadrivalent HPV vaccine Randomised blinded controlled trial 0,2,6 months 7 months cLIA Geometric mean anti-HPV-6, 11, 16 and—18 antibody titres. Positivity to HPV 6, 11, 16 and 18 by PCR and CIN lesions. Any Condyloma VIN 1 or VaIN The vaccine was 92.8 and 100 % effective in preventing cervical intraepithelial neoplasia and external genital lesions related to vaccine HPV types, respectively.
Muñoz et al. (2009) [25] Multi-center trial Colombia, France, Germany, Philippines, Spain, Thailand, and the USA. Healthy Women aged 24–45 years n = 3819 Quadrivalent HPV vaccine Randomised, placebo-controlled, double-blind study At 0, 2 and 6 months Mean follow up 2.2 years HPV multiplex PCR testing Incidence of cervical and external genital disease related to HPV 6, 11, 16, or 18; and to HPV 16 or 18 alone The quadrivalent vaccine is effi cacious in women aged 24–45 years not infected with the relevant HPV types at enrolment.
Medina et al. (2010) [16] Multi center with Healthy Honduras girls 10–26 years n = 2067 Bivalent HPV-16/18 vaccine Randomised controlled observer blind trial (1:1) at 0, 1, and 6 months 7 months ELISA Safety and immunogenicity The vaccine was generally well tolerated and immunogenic among these girls.(GMT HPV-16 14,778.0 (95 % CI 12,668.5-17,238.7 and HPV 18 6149.1 (95 % CI 5314.5- 7114.7)
Bhatla et al. (2010) [19] Healthy Indian women of an older age group 18–35 years (n = 330) Bivalent HPV-16/18 Vaccine Double blinded randomized multi center trial at 0, 1, and 6 months 7 months VLP ELISA Geometric mean anti-HPV-16 and −18 antibody titres Vaccine was highly immunogenic and safe in this older population of women (GMT levels HPV-16 10226.5 (95 % CI 8847.1-11821.0) and HPV-18 3953.0 (95 % CI 3421.8-4566.8)
Neuzil et al. (2011) [27] Adolescent Vietnam girls 11–13 year n = 903 Quadrivalent HPV Open-label, cluster randomized, noninferiority study 3 doses of quadrivalent HPV vaccine on a standard dosing schedule (at 0, 2, and 6 months) and 3 alternative dosing schedules (at 0, 3, and 9 months; at 0, 6, and 12 months; or at 0, 12, and 24 months. 1 month after receipt of the third vaccine dose cLIA Geometric mean anti-HPV-6, 11,16 and −18 antibody titres Vaccine administration on standard and alternative schedules was immunogenic and well tolerated. Use of alternative dosing compared with a standard schedule did not result in inferior antibody concentrations.
Salif Sow et al. (2012) [14] African girls (Tanzanian and Senegalese) girls and young women, seronegative for human immunodeficiency virus (HIV) 10–25 years (n = 450), placebo (n = 226) HPV-16/18 AS04-adjuvanted vaccine Double blinded, randomized controlled (2:1) at 0, 1, and 6 months Up to 12 months VLP ELISA Geometric mean anti-HPV-16 and −18 antibody titers The vaccine was highly immunogenic with 100 % seropositive for both anti–HPV-16 and anti–HPV-18 antibodies and safety profile
Khatun et al. (2012) [18] Healthy adolescent Bangladesh girls 9–13 years n = 67 Bivalent HPV-16/18 vaccine Randomized controlled trial (3:1) 0, 1, 6 months 7 months ELISA Geometric mean anti-HPV-16 and −18 antibody titres Vaccine was well tolerated, and highly immunogenic
Schwarz et al. (2012) [17] Healthy Girls 10–14 years from 31 centers in Taiwan, Germany, Honduras, Panama, and Colombia HPV-16/18 AS04-adjuvanted Open label randomized trial at 0, 1, and 6 months Four year follow up ELISA Geometric mean anti-HPV-16 and −18 antibody titres The HPV-16/18 AS04-adjuvanted vaccine produces anti-HPV-16 and anti-HPV-18 antibody titers that are maintained for up to 4 years at higher levels than those in young women in whom vaccine efficacy against cervical lesions was demonstrated.
n = 1035
Brown et al. (2013) [22] Tanzanian females 10–25 years (n = 298) HPV-16/18 AS04-adjuvanted vaccine Sub-study nested within a Phase IIIb immunogenicity and safety trial of the HPV-16/18 AS04-adjuvanted vaccine at 0, 1, and 6 months Follow up to 12 months ELISA Geometric mean anti-HPV-16 and −18 antibody titers Parasitic infections were common overall, the vaccine induced high HPV-16/18 GMTs, (HPV 16 10,786 EU/mL (95 % CI 9126–12,747), and HPV-18 3701 EU/mL (95 % CI 3156–4340). There was no evidence of a reduction in HPV-16 or HPV-18 GMT at Month 7 or Month 12 follow-up visits among participants with helminths or malaria.
LaMontagne et al. (2013) [28] Vietnam girls 11–13 year n = 903 Quadrivalent HPV vaccine Open-label, cluster randomized, noninferiority study 3 doses of quadrivalent HPV vaccine on a standard dosing schedule (at 0, 2, and 6 months) and 3 alternative dosing schedules (at 0, 3, and 9 months; at 0, 6, and 12 months; or at 0, 12, and 24 months. >2 years follow up cLIA Geometric mean anti-HPV-6, 11,16 and −18 antibody titres. HPV vaccine dose- timing, and extended schedules do not produce inferior immune responses. In addition, 2 doses of HPV vaccine delivered at 0 and 12 months might afford similar protection
Nakalembe et al. (2014) [21] Ugandan girls 10–16 years HPV-16/18 AS04-adjuvanted vaccine Cross-sectional study follow up on girls vaccinated in 2010 in an HPV demonstration project 0,1 and 6 months 18 months post vaccination Multiplex HPV serology Median Flourescent intenstity The AS04-Adjuvanted HPV-16/18 vaccinated girls showed a higher level of antibodies to HPV-16/18(HPV-16 4691 95 % CI: 4438–4958 among the vaccinated compared to 218 95 % CI: 190–252 among the unvaccinated girls; HPV-18 1326 95 % CI: 1470–1776 among the vaccinated compared to 103 95 % CI: 88–121) among unvaccinated girls) and other non-vaccine hrHPV types compared to the unvaccinated girls.
(n = 404)
LaMontagne et al. (2014) [29] Ugandan girls 10–17 years HPV-16/18 AS04-adjuvanted vaccine Cross-sectional follow-up study. Girls vaccinated in a government-run HPV vaccination demonstration program 0,1 and 6 months At month 36 post vaccination VLP ELISA Geometric mean anti-HPV-16 and −18 antibody titres The immunogenicity with less than three doses did not meet a priori non-inferiority thresholds. However, antibody levels measured ≥24 months after last dose were similar to those of adult women where efficacy has been demonstrated (GMTs HPV161-dose = 230 HPV16 2-dose = 808,and HPV16 3-dose = 1607; HPV181-dose = 87, HPV182-dose = 270, and HPV183-dose = 296 EU/mL) The GMT ratio for 2:3 doses was 0.50 for HPV16 and 0.68 for HPV18).
One dose n = 230, 2 doses n = 808, 3 doses n = 1608
Skinner et al. (2014) [26] Phillipines >25 year old women n = 5752 HPV-16/18 AS 04-adjuvanted vaccine double-blind, randomised controlled trial At 0, 1 and 6 months Mean follow up 40.3 months HPV DNA 6-month persistent infection with HPV 16 or HPV 18 (HPV 16/18) or CIN grade 1 or greater (CIN1+) associated with HPV 16/18. The HPV 16/18 vaccine is efficacious against infections and cervical abnormalities associated with the vaccine types, as well as infections with the non-vaccine HPV types 31 and 45.