BACKGROUND
Human papillomavirus (HPV) vaccination programmes were first implemented in several countries worldwide in 2007. We did a systematic review and meta-analysis to assess the population-level consequences and herd effects after female HPV vaccination programmes, to verify whether or not the high efficacy reported in randomised controlled clinical trials are materialising in real-world situations.


METHODS
We searched the Medline and Embase databases (between Jan 1, 2007 and Feb 28, 2014) and conference abstracts for time-trend studies that analysed changes, between the pre-vaccination and post-vaccination periods, in the incidence or prevalence of at least one HPV-related endpoint: HPV infection, anogenital warts, and high-grade cervical lesions. We used random-effects models to derive pooled relative risk (RR) estimates. We stratified all analyses by age and sex. We did subgroup analyses by comparing studies according to vaccine type, vaccination coverage, and years since implementation of the vaccination programme. We assessed heterogeneity across studies using I(2) and χ(2) statistics and we did trends analysis to examine the dose-response association between HPV vaccination coverage and each study effect measure.


FINDINGS
We identified 20 eligible studies, which were all undertaken in nine high-income countries and represent more than 140 million person-years of follow-up. In countries with female vaccination coverage of at least 50%, HPV type 16 and 18 infections decreased significantly between the pre-vaccination and post-vaccination periods by 68% (RR 0·32, 95% CI 0·19-0·52) and anogenital warts decreased significantly by 61% (0·39, 0·22-0·71) in girls 13-19 years of age. Significant reductions were also recorded in HPV types 31, 33, and 45 in this age group of girls (RR 0·72, 95% CI 0·54-0·96), which suggests cross-protection. Additionally, significant reductions in anogenital warts were also reported in boys younger than 20 years of age (0·66 [95% CI 0·47-0·91]) and in women 20-39 years of age (0·68 [95% CI 0·51-0·89]), which suggests herd effects. In countries with female vaccination coverage lower than 50%, significant reductions in HPV types 16 and 18 infection (RR 0·50, 95% CI 0·34-0·74]) and in anogenital warts (0·86 [95% CI 0·79-0·94]) occurred in girls younger than 20 years of age, with no indication of cross-protection or herd effects.


INTERPRETATION
Our results are promising for the long-term population-level effects of HPV vaccination programmes. However, continued monitoring is essential to identify any signals of potential waning efficacy or type-replacement.


FUNDING
The Canadian Institutes of Health Research.

Population-level impact and herd effects following human papillomavirus vaccination programmes: a systematic review and meta-analysis

There is an urgent need for effective countermeasures against the current emergence and accelerating expansion of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Induction of herd immunity by mass vaccination has been a very successful strategy for preventing the spread of many infectious diseases, hence protecting the most vulnerable population groups unable to develop immunity, for example individuals with immunodeficiencies or a weakened immune system due to underlying medical or debilitating conditions. Therefore, vaccination represents one of the most promising counter-pandemic measures to COVID-19. However, to date, no licensed vaccine exists, neither for SARS-CoV-2 nor for the closely related SARS-CoV or Middle East respiratory syndrome-CoV. In addition, a few vaccine candidates have only recently entered human clinical trials, which hampers the progress in tackling COVID-19 infection. Here, we discuss potential prophylactic interventions for SARS-CoV-2 with a focus on the challenges existing for vaccine development, and we review pre-clinical progress and ongoing human clinical trials of COVID-19 vaccine candidates. Although COVID-19 vaccine development is currently accelerated via so-called fast-track programs, vaccines may not be timely available to have an impact on the first wave of the ongoing COVID-19 pandemic. Nevertheless, COVID-19 vaccines will be essential in the future for reducing morbidity and mortality and inducing herd immunity, if SARS-CoV-2 becomes established in the population like for example influenza virus.

/pdf/the-long-road-toward-covid-19-herd-immunity-vaccine-platform-444t7ejuvb.pdf

The Long Road Toward COVID-19 Herd Immunity: Vaccine Platform Technologies and Mass Immunization Strategies.

BACKGROUND
Hepatitis E virus (HEV) is a leading cause of acute hepatitis. The long-term efficacy of a hepatitis E vaccine needs to be determined.


METHODS
In an initial efficacy study, we randomly assigned healthy adults 16 to 65 years of age to receive three doses of either a hepatitis E vaccine (vaccine group; 56,302 participants) or a hepatitis B vaccine (control group; 56,302 participants). The vaccines were administered at 0, 1, and 6 months, and the participants were followed for 19 months. In this extended follow-up study, the treatment assignments of all participants remained double-blinded, and follow-up assessments of efficacy, immunogenicity, and safety were continued for up to 4.5 years.


RESULTS
During the 4.5-year study period, 60 cases of hepatitis E were identified; 7 cases were confirmed in the vaccine group (0.3 cases per 10,000 person-years), and 53 cases in the control group (2.1 cases per 10,000 person-years), representing a vaccine efficacy of 86.8% (95% confidence interval, 71 to 94) in the modified intention-to-treat analysis, rather than (95% confidence interval, 71 to 84) [corrected]. Of the participants who were assessed for immunogenicity and were seronegative at baseline, 87% of those who received three doses of the hepatitis E vaccine maintained antibodies against HEV for at least 4.5 years; HEV antibody titers developed in 9% in the control group. The rate of adverse events was similar in the two groups.


CONCLUSIONS
Immunization with this hepatitis E vaccine induced antibodies against HEV and provided protection against hepatitis E for up to 4.5 years. (Funded by the Chinese Ministry of Science and Technology and others; ClinicalTrials.gov number, NCT01014845.).

Long-Term Efficacy of a Hepatitis E Vaccine ; 戊型肝炎疫苗的长期保护效果

Recent Progress on the Versatility of Virus-Like Particles

https://minerva-access.unimelb.edu.au/bitstream/handle/11343/252588/PIIS2214109X20302771.pdf

Domestic HPV vaccine price and economic returns for cervical cancer prevention in China: a cost-effectiveness analysis

Background The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase III clinical trial was conducted to evaluate the efficacy, safety, and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multicenter, randomized, double-blind trial started on November 22, 2012 in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receive three doses of the test or control (hepatitis E) vaccine at months 0, 1, and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received three doses of the vaccine. This report presents data from a prespecified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval = 55.6% to 100.0%, 0 of 3306 in the vaccine group vs 10 of 3296 in the control group) and 97.8% (95% confidence interval = 87.1% to 99.9%, 1 of 3240 vs 45 of 3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The E coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18-associated high-grade genital lesions and persistent infection in women.

/pdf/efficacy-safety-and-immunogenicity-of-an-escherichia-coli-129z9uobgm.pdf

Efficacy, Safety, and Immunogenicity of an Escherichia coli-Produced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial

Statistics regarding HPV prevalence and cervical cancer rates in rural China are high, however, low levels of HPV awareness and HPV-related knowledge pose a great challenge for cervical cancer control. The authors conducted an educational intervention study, which was embedded in a cervical cancer screening project in Yangcheng county, Shanxi Province, China from October to December, 2011 and was designed to assess the short-term effectiveness of a hospital-based, brief, HPV-focused session on rural Chinese women’s knowledge and attitudes. Student’s t-test was used when comparing quantitative variables. Chi-squared test or Fisher’s exact tests was used when comparing qualitative variables. We found that following the intervention, significant increases were detected in awareness regarding HPV (5.9 % vs. 59 %, p < 0.001) and cervical cancer (63.0 % vs. 89.2 %, p < 0.001). Changes were also observed regarding women’s intention to vaccinate themselves (82.0 % vs. 89.0 %, p = 0.001) and their daughters (82.9 % vs. 88.0 %, p = 0.011), although the impact was more modest compared with the impact on change of awareness. Among women who were aware of HPV, 60.3 % knew that cervical cancer is related to HPV, while only 5.0 % knew the relationship between HPV and genital warts after the educational intervention. Educational campaigns, particularly those targeting women with limited education and poor access to public media or other educational channels are needed to improve knowledge regarding HPV in the general population.

/pdf/effect-of-a-group-educational-intervention-on-rural-chinese-3njdwufagl.pdf

Ba-Yi Li

Papers

Efficacy, Safety, and Immunogenicity of an Escherichia coli-Produced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial

Effect of a group educational intervention on rural Chinese women’s knowledge and attitudes about human papillomavirus (HPV) and HPV vaccines