Vaccines for COVID-19: Where do we stand in 2021?

As of July 2021, over 3 billion doses of a COVID-19 vaccines have been administered globally, and there are now 19 COVID-19 vaccines approved for use in at least one country. Several of these have been shown to be highly effective both in clinical trials and real-world observational studies, some of which have included special populations of interest. A small number of countries have approved a COVID-19 vaccine for use in adolescents or children. These are laudable achievements, but the global vaccination effort has been challenged by inequitable distribution of vaccines predominantly to high income countries, with only 0.9% of people in low-income countries having received at least one dose of a COVID-19 vaccine. Addressing this inequity is of critical importance and will result in better control of SARS-CoV-2 globally. Other challenges include: the reduced protection from COVID-19 vaccines against some strains of SARS-CoV-2, necessitating the development of variant specific vaccines; and uncertainties around the duration of protection from vaccine-induced immunity.

COVID-19 vaccines - are we there yet?

The novel coronavirus SARS-CoV-2, the cause of the COVID-19 pandemic, is a highly infectious human respiratory pathogen to which the global population had no prior immunity. The virus will likely continue to cause significant morbidity until there is a broadly effective vaccine As of mid-December 2020, more than 200 COVID-19 vaccine candidates are in development and 11 have entered phase III clinical trials globally. All generate immunity to the viral spike glycoprotein Three vaccine candidates have agreements for procurement and use in Australia if efficacy and safety requirements are met - one protein-based vaccine, one vaccine using a simian-derived adenovirus vector and one messenger RNA vaccine. The latter two vaccines have published interim analyses and efficacy results of their phase III trials. The messenger RNA vaccine is being rolled out in the UK, USA and Canada Significant uncertainties remain. How well will some of those at highest risk of severe disease (such as older people aged >75 years and those with immunocompromising conditions) be protected by a vaccine, and for how long? Also, to what extent will vaccination protect against infection? This will determine the degree of indirect 'herd' protection needed through broad vaccine coverage of younger age groups.

Vaccines for COVID-19: The current state of play.

There is a strong consensus globally that a COVID-19 vaccine is likely the most effective approach to sustainably controlling the COVID-19 pandemic. An unprecedented research effort and global coordination has resulted in a rapid development of vaccine candidates and initiation of trials. Here, we review vaccine types, and progress with 10 vaccine candidates against SARS-CoV-2 - the virus that causes COVID-19 - currently undergoing early phase human trials. We also consider the many challenges of developing and deploying a new vaccine on a global scale, and recommend caution with respect to our expectations of the timeline that may be ahead.

Effectiveness of 7- and 13-Valent Pneumococcal Conjugate Vaccines in a Schedule Without a Booster Dose: A 10-Year Observational Study.

Background: Unique among high-income countries, Australia has used a 3 + 0 schedule (3 primary doses, no booster) for infant pneumococcal conjugate vaccine (PCV) since January 2005, initially 7 valent (PCV7) then 13 valent (PCV13) from July 2011. We measured vaccine effectiveness (VE) of both PCVs against invasive pneumococcal disease (IPD) using 2 methods. Methods: Cases were IPD notifications to the national surveillance system of children eligible for respective PCVs. For case-control method, up to 10 age-matched controls were derived from the Australian Childhood Immunisation Register. For indirect cohort method, controls were IPD cases due to serotypes not in PCVs. VE was calculated as (1 - odds ratio [OR]) × 100 by logistic regression. VE waning was estimated as odds of vaccine type (VT) IPD in consecutive 12-month periods post-dose 3. Results: Between 2005 and 2014, there were 1209 and 308 IPD cases in PCV7-eligible and PCV13-eligible cohorts, respectively. Both methods gave comparable VE estimates. In infants, VE for 3 doses against VT IPD was 92.9% (95% confidence interval [CI], 27.7% to 99.3%) for PCV7 and 86.5% (95% CI, 11.7% to 97.9%) for PCV13. From 12 months post-dose 3, the odds of VT IPD by 24-36 months increased significantly for PCV7 (5.6, 95% CI, 1.2-25.4) and PCV13 (5.9, 95% CI, 1.0-35.2). Conclusions: For both PCVs in a 3 + 0 schedule, despite similar VE, progressive increase in breakthrough cases only occurred post-PCV13. This supports the importance of a booster dose of PCV13 in the second year of life to maintain protection.

Long-term Impact of a "3 + 0" Schedule for 7- and 13-Valent Pneumococcal Conjugate Vaccines on Invasive Pneumococcal Disease in Australia, 2002-2014.

BACKGROUND: Australia introduced universal 7-valent pneumococcal conjugate vaccine (PCV7) from 2005, replaced by 13-valent PCV (PCV13) in 2011, uniquely among high-income countries giving doses at 2, 4, and 6 months (3 + 0 schedule). Data on impact of a timely 3 + 0 PCV schedule with high coverage are sparse, with none for PCV13. METHODS: We used national surveillance of invasive pneumococcal disease (IPD) from 2002 for baseline and appropriate later comparison periods to calculate incidence rate ratios (IRRs) by serotype and age using a Poisson model. PCV coverage was assessed from the Australian Childhood Immunisation Register. RESULTS: After 9 years of timely 3-dose PCV coverage of >92%, all-age IPD in Australia almost halved (IRR, 0.53; 95% confidence interval [CI], .50-.57), but differed by PCV era. Reductions in IPD due to vaccine serotypes from PCV7 (IRR, 0.20; CI, .17-.22) were about 2-fold greater than for IPD due to extra serotypes in PCV13 (13v-non7v) in a similar period (IRR, 0.58; CI, .51-.66). Post-PCV13 declines in serotype 19A IPD in persons aged <2 years (IRR, 0.23; CI, .13-.35) and ≥2 years (IRR, 0.35; CI, .28-.44) differed from other 13v-non7v IPD (IRR, 0.73; CI, .35-1.48 for those aged <2 years and IRR, 0.96; CI, .81-1.15 for those ≥2 years). Meningitis due to vaccine serotypes nearly disappeared in children eligible for 3 PCV13 doses. IPD due to non-PCV13 serotypes increased by 30% compared with 76% for non-PCV7 serotypes in equivalent period of vaccine use. CONCLUSIONS: Reductions in vaccine-type IPD post-PCV13 were inferior to Australian experience with PCV7 and reports from high-income countries giving a PCV booster dose. Applicability of findings to other settings would depend on age of IPD onset, serotype profile, and timeliness of vaccination.

Systematic Review and Meta-analysis of Indirect Protection Afforded by Vaccinating Children Against Seasonal Influenza: Implications for Policy.

BACKGROUND: Universal childhood vaccination is a potential solution to reduce seasonal influenza burden. METHODS: We reviewed systematically the literature on "herd"/indirect protection from vaccinating children aged 6 months to 17 years against influenza. RESULTS: Of 30 studies included, 14 (including 1 cluster randomized controlled trial [cRCT]) used live attenuated influenza vaccine, 11 (7 cRCTs) used inactivated influenza vaccine, and 5 (1 cRCT) compared both vaccine types. Twenty of 30 studies reported statistically significant indirect protection effectiveness (IPE) with point estimates ranging from 4% to 66%. Meta-regression suggests that studies with high quality and/or sufficiently large sample size are more likely to report significant IPE. In meta-analyses of 6 cRCTs with full randomization (rated as moderate quality overall), significant IPE was found in 1 cRCT in closely connected communities where school-aged children were vaccinated: 60% (95% confidence interval [CI], 41%-72%; I2 = 0%; N = 2326) against laboratory-confirmed influenza, and 3 household cRCTs in which preschool-aged children were vaccinated: 22% (95% CI, 1%-38%; I2 = 0%; N = 1903) against acute respiratory infections or influenza-like illness. Significant IPE was also reported in a large-scale cRCT (N = 8510) that was not fully randomized, and 3 ecological studies (N > 10000) of moderate quality including 36% reduction in influenza-related mortality among the elderly in a Japanese school-based program. Data on IPE in other settings are heterogeneous and lacked power to draw a firm conclusion. CONCLUSIONS: The available evidence suggests that influenza vaccination of children confers indirect protection in some but not all settings. Robust, large-scaled studies are required to better quantify the indirect protection from vaccinating children for different settings/endpoints.

Epidemiology of invasive meningococcal B disease in Australia, 1999-2015: priority populations for vaccination.

OBJECTIVES: To describe trends in the age-specific incidence of serogroup B invasive meningococcal disease (IMD) in Australia, 1999-2015. DESIGN, SETTING, PARTICIPANTS: Analysis in February 2017 of de-identified notification data from the Australian National Notifiable Diseases Surveillance System of all notifications of IMD in Australia with a recorded diagnosis date during 1999-2015.Major outcomes: IMD notification rates in Australia, 1999-2015, by age, serogroup, Indigenous status, and region. RESULTS: The incidence of meningococcal serogroup B (MenB) disease declined progressively from 1.52 cases per 100 000 population in 2001 to 0.47 per 100 000 in 2015. During 2006-2015, MenB accounted for 81% of IMD cases with a known serogroup; its highest incidence was among infants under 12 months of age (11.1 [95% CI, 9.81-12.2] per 100 000), children aged 1-4 years (2.82 [95% CI, 2.52-3.15] per 100 000), and adolescents aged 15-19 years (2.40 [95% CI, 2.16-2.67] per 100 000). Among the 473 infants under 2 years of age with MenB, 43% were under 7 months and 69% under 12 months of age. The incidence of meningococcal serogroup C (MenC) disease prior to the introduction of the MenC vaccine in 2003 was much lower in infants than for MenB (2.60 cases per 100 000), the rate peaking in people aged 15-19 years (3.32 per 100 000); the overall case fatality rate was also higher (MenC, 8%; MenB, 4%). The incidence of MenB disease was significantly higher among Indigenous than non-Indigenous Australians during 2006-2015 (incidence rate ratio [IRR], 3.8; 95% CI, 3.3-4.5). CONCLUSIONS: Based on disease incidence at its current low endemic levels, priority at risk age/population groups for MenB vaccination include all children between 2 months and 5 years of age, Indigenous children under 10 years of age, and all adolescents aged 15-19 years. Given marked variation in meningococcal disease trends over time, close scrutiny of current epidemiologic data is essential.

Determining the contribution of Streptococcus pneumoniae to community-acquired pneumonia in Australia.

OBJECTIVE: To evaluate trends in the proportion and severity of community-acquired pneumonia (CAP) attributable to Streptococcus pneumoniae (pneumococcus) in Australians aged 18 years and over. STUDY DESIGN: Systematic review with unpublished data from the largest study. DATA SOURCES: Multiple key bibliographic databases to June 2016. STUDY SELECTION: Australian studies on the aetiology of CAP in adults. DATA SYNTHESIS: In the 12 studies identified, pneumococcus was the most common cause of CAP. Four studies were assessed as being of good quality. Participants in two studies were predominantly non-Indigenous (n = 991); the proportion of pneumococcal CAP cases declined from 26.4% in 1987-88 to 13.9% in 2004-06, and the proportion with bacteraemia decreased from 7.8% to 3.8%. In two studies with predominantly Indigenous participants (n = 252), the proportion with pneumococcal bacteraemia declined from 6.8% in 1999-2000 to 4.2% in 2006-07. In the largest study (n = 885; 2004-06), 50.8% (60/118) of pneumococcal CAP occurred in people who were ≥ 65 years old. Among patients aged ≥ 65 years, intensive care unit admission and death were more common in patients who were ≥ 85 years old compared with younger patients (12.5% v 6.8%; 18.8% v 6.8% respectively), and also more common in the 19 patients with bacteraemia than in those without it (15.8% v 2.6%; 10.5% v 7.9% respectively). Of 17 cases of bacteraemia serotyped, 12 were due to 13-valent pneumococcal conjugate vaccine (13vPCV) serotypes and three to additional serotypes in 23-valent pneumococcal polysaccharide vaccine (23vPPV). CONCLUSIONS: Available data suggest that the proportion of CAP attributable to pneumococcus (both bacteraemic and non-bacteraemic) has been declining in Australian adults. Should 13vPCV replace the 23vPPV currently funded by the National Immunisation Program for persons aged ≥ 65 years, surveillance to track non-bacteraemic pneumococcal CAP will be essential to evaluate the impact.

Australian vaccine preventable disease epidemiological review series: Influenza 2006 to 2015.

INTRODUCTION: Influenza is a major contributor to the preventable health burden of Australians each year. The National Immunisation Program provides influenza vaccine for those at highest risk of severe disease. This review of influenza epidemiology examines current data on influenza disease burden in Australia, in the context of several comparable countries having programs with much broader eligibility for influenza vaccine in children. METHODS: Influenza notifications (2006-2015), hospitalisations, and deaths (2006-2013) were sourced and age-specific rates calculated. Comparisons were made across age groups in the pre-pandemic, pandemic, and post-pandemic periods and by Indigenous and non-Indigenous status. RESULTS: The 2009 pandemic year and the 2012 non-pandemic season resulted in the highest rates of notification, hospitalisation and death. Influenza notification rates were 4.0 times higher and hospitalisation rates 2.1 times higher during 2011-2013 compared with 2006-2008. Death rates varied widely, but peaks corresponded to high-activity seasons. Influenza hospitalisation rates were highest among those aged <5 and ≥65 years, but influenza-attributable deaths were identified primarily in those aged ≥75 years. Significantly higher notification and hospitalisation rates were seen for all Indigenous people, but higher death rates were largely restricted to the 2009 pandemic year. CONCLUSIONS: Based on notifications, hospitalisations and deaths, burden of disease from influenza is highest at the extremes of life and is significantly higher among Indigenous people of all ages. This pattern of disease burden warrants consideration of widened eligibility for influenza vaccine under the National Immunisation Program to all Indigenous people and all children less than 5 years of age.

Impact of pneumococcal polysaccharide vaccine in people aged 65 years or older.

OBJECTIVE: To evaluate the impact and effectiveness of the 23-valent polysaccharide pneumococcal vaccine (23vPPV) in ≥ 65-year-old Australians in the context of concurrent 7-valent pneumococcal conjugate vaccine (7vPCV) use in infants. DESIGN, PATIENTS AND SETTING: Ecological analysis of trends in invasive pneumococcal disease (IPD) notification rates and vaccine effectiveness estimation using the screening method, using data on Australians aged ≥ 65 years (23vPPV funded) and 50-64 years (23vPPV not funded). INTERVENTION: National 23vPPV program for people aged ≥ 65 years and national 7vPCV program for infants, both commencing in 2005. MAIN OUTCOME MEASURES: IPD incidence rate ratios, 2002-2004 to 2010-2011, and 23vPPV effectiveness against 23vPPV-type IPD. RESULTS: The proportion of people aged ≥ 65 years who were vaccinated within the previous 5 years in jurisdictions excluding Victoria ranged from 41% to 64% over the study period, with no clear trend over time. Incidence rate ratios in the ≥ 65-year age group were 0.11 (95% CI, 0.09-0.14) for 7vPCV serotypes, 1.64 (95% CI, 1.41-1.91) for 23vPPV-non-7vPCV serotypes and 2.07 (95% CI, 1.67-2.57) for non-23vPPV serotypes. The incidence rate ratio for total IPD was 0.65 (95% CI, 0.59-0.71) for people aged ≥ 65 years, and 0.80 (0.71-0.90) for people aged 50-64 years. The estimate of 23vPPV effectiveness was 61.1% (95% CI, 55.1%-66.9%). CONCLUSIONS: The greater reduction in IPD among ≥ 65-year-olds compared with 50-64-year-olds did not reach statistical significance. However, vaccine effectiveness was significant. Greater reductions in IPD in ≥ 65-year-olds would be expected from the indirect effects of using 13-valent pneumococcal conjugate vaccine in infants (introduced for Australian infants in 2011) and an increase in 23vPPV coverage.

ATAGI targeted review 2023: Vaccination for preventing influenza in Australia.

Abstract: Annual seasonal influenza epidemics cause substantial disease and economic burden worldwide. During the coronavirus disease 2019 (COVID-19) pandemic in 2020 and 2021, influenza activity significantly declined. However, influenza resurged in Australia following the relaxation of non-pharmaceutical interventions, with increased influenza virus circulation in early 2022 coinciding with the SARS-CoV-2 Omicron BA.2 variant wave. Together with other respiratory virus diseases, these disease impacts on the Australian population and healthcare system have re-emphasised the importance of influenza vaccination and control. We aim to provide an overview of the current seasonal influenza vaccination program in Australia and summarise evidence and considerations underpinning potential future immunisation strategies. Influenza causes disproportionately higher morbidity and mortality in young children and older adults. Other populations at elevated risk from influenza include Aboriginal and Torres Strait Islander peoples, pregnant women, and people with certain underlying medical conditions. All Australians aged ≥ 6 months are recommended to receive influenza vaccine every year. The National Immunisation Program (NIP) provides free vaccine for eligible at-risk populations. While approximately 70% of older adults had received influenza vaccine in 2022, coverage in other age groups remains suboptimal. There are several key unmet needs and challenges, but also potential strategies for enhancing the influenza vaccination program in Australia. Improved monitoring and evaluation, including the use of relevant linked datasets for such purposes, is imperative to better understand variations in coverage and vaccination impact in specific populations. Adoption of evidence-based strategies, such as culturally appropriate resources that consider the characteristics of diverse Australian populations, may also help to achieve higher vaccine coverage rates. Additionally, greater vaccine uptake across the population could be facilitated by expanding the NIP-eligible population where cost-effective, and adopting the use of more effective and different types of vaccines when available.

Vaccine preventable diseases and vaccination coverage in Aboriginal and Torres Strait Islander people, Australia 2006-2010.

This report outlines the major positive impacts of vaccines on the health of Aboriginal and Torres Strait Islander people from 2007 to 2010, as well as highlighting areas that require further attention. Hepatitis A disease is now less common in Aboriginal and Torres Strait Islander children than in their non-Indigenous counterparts. Hepatitis A vaccination for Aboriginal and Torres Strait Islander children was introduced in 2005 in the high incidence jurisdictions of the Northern Territory, Queensland, South Australia and Western Australia. In 2002­2005, there were 20 hospitalisations for hepatitis A in Aboriginal and Torres Strait Islander children aged<5 years--over 100 times more common than in other children--compared to none in 2006/07­2009/10. With respect to invasive pneumococcal disease (IPD), there has been a reduction of 87% in notifications of IPD caused by serotypes contained in 7-valent pneumococcal conjugate vaccine (7vPCV) since the introduction of the childhood 7vPCV program among Aboriginal and Torres Strait Islander children. However, due to a lower proportion of IPD caused by 7vPCV types prior to vaccine introduction, the decline in total IPD notifications has been less marked in Aboriginal and Torres Strait Islander children than in other children. Higher valency vaccines (10vPCV and 13vPCV) which replaced 7vPCV from 2011 are likely to result in a greater impact on IPD and potentially also non-invasive disease, although disease caused by non-vaccine serotypes appears likely to be an ongoing problem. Among Aboriginal and Torres Strait Islander people aged ≥50 years, there have been recent increases in IPD, which appear related to low vaccination coverage and highlight the need for improved coverage in this high-risk target group. Since routine meningococcal C vaccination for infants and the high-school catch-up program were implemented in 2003, there has been a significant decrease in cases caused by serogroup C. However, the predominant serogroup responsible for disease remains serogroup B, and Aboriginal and Torres Strait Islander children have significantly higher incidence of serogroup B disease than other children. A vaccine against meningococcus type B has now been licensed in Australia. The decline in severe rotavirus disease after vaccine introduction in 2007 was less marked in Aboriginal and Torres Strait Islander children than in other children. By far the highest hospitalisation rates continue to occur among Aboriginal and Torres Strait Islander children in the Northern Territory. Consideration of the role of age cut-offs and 2-dose versus 3-dose schedules may be necessary. Genotype surveillance is critically important to allow detection of any possible emergence of genotypes for which there is lower vaccine-derived immunity. Although Haemophilus influenzae type b disease rates have decreased significantly since the introduction of vaccines in 1993, the plateauing of rates in Aboriginal and Torres Strait Islander children, and increasing disparity with other children, are concerning. While it is possible that higher disease rates in young infants could be associated with the later age of protection from the newer 4-dose schedule, it is also possible that higher vaccine immunogenicity will result in reduced carriage. Close monitoring is important to detect any re-emergence of Hib disease as soon as possible. Pandemic and seasonal influenza and pneumonia are other diseases with comparatively higher rates in Aboriginal and Torres Strait Islander people. For Aboriginal and Torres Strait Islander people aged≥50 years, it is unclear whether or not there has been a decline in influenza hospitalisations since the start of the National Indigenous Pneumococcal and Influenza Immunisation Program in 1999, but hospitalisation rates are still higher in Aboriginal and Torres Strait Islander people. Achieving high coverage in those aged≥15 years should now be a priority. A prolonged mumps outbreak occurred in 2007/2008 predominantly affecting Aboriginal and Torres Strait Islander adolescents and young adults in north-western Australia. A potential contributor to this mumps outbreak was greater waning of immunity after receipt of the first dose of mumps-containing vaccine at 9, rather than 12, months of age in the Northern Territory in the 1980s and 1990s. However, outbreaks in Australia and overseas have subsided without additional boosters being routinely implemented. Pertussis epidemics continue to occur in Australia and affect both Aboriginal and Torres Strait Islander and other people. Parents are now encouraged to have their infant's first vaccination given at 6 weeks of age, instead of the usual 2 months, and this is being successfully implemented for Aboriginal and Torres Strait Islander and other infants. Timely provision of the 4- and 6-month doses remains very important. High coverage for standard vaccines, poor timeliness of vaccination and lower coverage for 'Indigenous only' vaccines are continuing features of vaccination programs for Aboriginal and Torres Strait Islander people. There have been some improvements in vaccination timeliness in recent years for all children, but disparities remain between Aboriginal and Torres Strait Islander and other children. Poor timeliness reduces the potential benefits of vaccination, most importantly for pneumococcal, Hib and rotavirus vaccines in infants. The age cut-offs for rotavirus vaccines present a particular challenge for timely vaccination, limiting the capacity for catching up on late vaccination and resulting in lower overall coverage. This is more pronounced for the 3-dose than for the 2-dose rotavirus schedule. Coverage for vaccines recommended only for Aboriginal and Torres Strait Islander children continues to remain substantially lower than that for universal vaccines. This underlines the importance of immunisation providers establishing the Indigenous status of their clients, so that additional vaccines are offered as appropriate. The absence of any coverage data for Aboriginal and Torres Strait Islander adolescents, or for adults since 2004/2005, is a substantial obstacle to implementing and improving programs in these age groups.

ATAGI Targeted Review 2021: the national COVID-19 vaccination program.

Abstract: The overarching goal of the Australian coronavirus disease 2019 (COVID-19) vaccination program has been to protect all people in Australia from the harm caused by the novel coronavirus SARS-CoV-2. This review reflects on the role of the Australian Technical Advisory Group on Immunisation (ATAGI) in the national COVID-19 vaccination program, in terms of the initial programmatic and clinical recommendations in the evolving context of evidence relating to the disease and vaccines, epidemiology, and the program rollout. To fulfil the obligation to provide evidence-based advice to the Minister for Health and Aged Care on the safe, effective and equitable use of COVID-19 vaccines, ATAGI has worked closely with other agencies and committees such as the Therapeutic Goods Administration (TGA) and the Communicable Diseases Network Australia. ATAGI recommendations have sought to optimise the use of the available vaccine doses in achieving the objectives of preventing serious illness and death from COVID-19 while addressing any emerging safety signals following program commencement on 22 February 2021. As of mid-November 2021, the use of COVID-19 vaccines in children aged 5 to 11 years was being considered by the TGA and ATAGI; and emerging evidence, in areas such as use of heterologous vaccine schedules and co-administration with other vaccines, was under review. Despite unprecedented challenges which the delivery of mass COVID-19 vaccination presented to health systems globally, in Australia much was achieved in 2021 with over 90% coverage for primary doses in the vaccine-eligible population. Evaluation, using high quality data and assessment methods, of vaccination program outcomes-such as coverage, vaccine effectiveness and impact-is key to determine whether program objectives have been achieved and where gaps remain. Reflecting on the lessons learned so far would help further improve the national COVID-19 vaccination program and would also benefit programs for other routine vaccines and planning for future pandemics.

ATAGI Targeted Review 2022: Vaccination for prevention of herpes zoster in Australia.

Abstract: In November 2016, herpes zoster (HZ) vaccination for older adults, using the live-attenuated zoster vaccine (Zostavax; ZVL) was added to the Australian National Immunisation Program (NIP) with the aim of reducing morbidity from HZ and its complications, particularly for people at increased risk. Prior to the program, there were on average 5.6 cases of HZ per 1,000 persons annually in Australia, with highest risk of disease in older and in immunocompromised people. The burden of complications of HZ, such as post-herpetic neuralgia (PHN), was also highest in older and immunocompromised groups. No formal comprehensive program evaluation has been undertaken since program commencement. This review examined published literature and available vaccine administration data to summarise the evidence and considerations underpinning current use of HZ vaccines and potential future program directions in Australia. There have been modest reductions in the incidence of HZ and its complications since program introduction. However, five years into the program, challenges remain, including suboptimal vaccine coverage and significant safety concerns arising from inadvertent use of ZVL in immunocompromised people, who are contraindicated to receive this vaccine. This reduces opportunities to offset the burden of HZ-related disease. The recombinant subunit zoster vaccine (Shingrix; RZV), first registered in Australia in 2018, became available on the Australian market in June 2021. This vaccine has higher efficacy than ZVL and, as a non-live vaccine, can be used in both immunocompetent and immunocompromised people. RZV has potential to address the unmet needs of at-risk population groups. However, it has not yet demonstrated cost-effectiveness for inclusion as a funded vaccine under the NIP. The Australian HZ vaccination program has had limited effectiveness in meeting its aim in highest risk groups. Future options and challenges anticipated in using vaccination to reduce the burden of HZ and its complications are discussed in this review.

Scientific evidence supporting recommendations on the use of the 9-valent HPV vaccine in a 2-dose vaccine schedule in Australia.

The Australian Technical Advisory Group on Immunisation (ATAGI) updated recommendations on the use of human papillomavirus (HPV) vaccines in the Australian Immunisation Handbook in 2018, regarding the use of the recently available 9-valent (9vHPV) vaccine, Gardasil 9, and a 2-dose schedule for young adolescents for HPV vaccines. This report provides an overview of the relevant scientific evidence that underpinned these updated recommendations. The 9vHPV vaccine includes 5 HPV types (HPV 31, 33, 45, 52 and 58) additional to the 4 that are also covered by the 4vHPV (Gardasil) vaccine (HPV 6,11,16,18). Accordingly, the 9vHPV vaccine is expected to prevent an additional 15% of cervical cancers and up to 20% of other HPV-related cancers. Non-inferior antibody responses after two 9vHPV vaccine doses given 6-12 months apart in girls and boys aged 9-14 years compared to women aged 16-26 years after three doses support the 2-dose schedule for adolescents of this age group. In clinical trials 9vHPV vaccine was well-tolerated with a similar safety profile to 4vHPV vaccine. The switch to 9vHPV vaccine and a 2-dose schedule is anticipated to improve public acceptability of the program and reduce HPV-related disease in the long-term.

Long-term Vaccine Impact on Invasive Pneumococcal Disease Among Children With Significant Comorbidities in a Large Australian Birth Cohort.

BACKGROUND: Little is known about long-term invasive pneumococcal disease (IPD) incidence in children with risk factors (RFs) in populations with high coverage pneumococcal conjugate vaccine (PCV) programs. We measured IPD burden and changes with PCV use in children by RF status. METHODS: A retrospective cohort of all live births in 2001-2012 in New South Wales, Australia was linked to IPD, hospitalization and death data. RFs were identified from International Classification of Diseases codes in linked hospitalizations. For each RF adjusted hazard ratios (aHRs, using Cox models), population attributable fractions (PAFs) and changes post-PCV relative to baseline for IPD were calculated. RESULTS: One-thousand two-hundred fifty-one IPD cases occurred in ~1.1 million children in 12-year study cohort. The 75,404 children (6.8% of cohort) with RFs accounted for 255 (20.4%) IPD cases [rate (per 100,000 person-years) of 61 compared with 14 in no RFs]. Asthma was most common RF (n = 41,074; 3.6%) but highest IPD risk was in 2452 children (0.2%) with immunosuppression, splenic dysfunction or breach in cerebrospinal fluid barrier (aHR~20; PAF 0.7-1.8%) versus asthma (aHR 5.3; PAF 14.8%). Compared with 2001-2004 birth cohort (baseline), IPD incidence in PCV-eligible 2009-2012 birth cohort was 78% (95% confidence interval: -72% to -82%) less in children without RFs. IPD declined nonsignificantly (13%; 95% confidence interval: -70% to +138%) in highest IPD risk group, but by 67% (-43% to -82%) in children with other RFs. CONCLUSIONS: By 8 years of universal PCV, IPD incidence reduced significantly in all children except in the 0.2% at highest risk, for whom antibiotic prophylaxis and additional vaccine doses are recommended but compliance and effectiveness remain uncertain.

ATAGI 2023 Annual Statement on Immunisation.

The Australian Technical Advisory Group on Immunisation (ATAGI) 2023 Annual Statement on Immunisation is the third publication in this series. It highlights the key successes, trends and challenges in the use of vaccines and control of vaccine preventable diseases (VPDs) in Australia in 2022. It also signals ATAGI's priority actions for addressing key issues for 2023 and beyond.

A review of the efficacy of human Q fever vaccine registered in Australia.

BACKGROUND: Q fever remains an important occupational zoonosis in rural Australia. Although Q fever vaccine is recommended in high-risk occupational groups, its availability has been limited in recent years. METHOD: A literature review of the efficacy of the human Q fever vaccine registered in Australia was conducted. RESULTS: Seven relevant vaccine efficacy studies were identified but no large double-blind, randomised, placebo-controlled studies have been conducted. Vaccine efficacy has ranged from 83-100% but limitations of study designs hamper a precise estimate of vaccine efficacy. CONCLUSION: Despite the shortcomings of efficacy studies, the Q fever vaccine available in Australia has considerable protective benefit in established high-risk environments, particularly of an occupational nature.