Health economic analyses of secondary vaccine effects: a systematic review and policy insights.

INTRODUCTION: Numerous analyses demonstrate substantial health-economic impacts of primary vaccine effects (preventing or mitigating clinical manifestations of the diseases they target), but vaccines may also be associated with secondary effects, previously known as nonspecific, heterologous, or off-target effects. AREAS COVERED: We define key concepts to distinguish primary and secondary vaccine effects for health economic analyses, summarized terminology used in different fields, and perform a systematic review of health economic analyses focused on secondary vaccine effects (SVEs). EXPERT OPINION: Health economists integrate evidence from multiple fields, which often use incomplete or inconsistent definitions. Like regulators and policy makers, health economists require high-quality evidence of specific effects. Consistent with the limited evidence on mechanisms of action for SVEs, the associated health economic literature remains highly limited, with 4 studies identified by our systematic review. The lack of specific and well-controlled evidence that supports quantification of specific SVEs limits the consideration of these effects in vaccine research, development, regulatory, and recommendation decisions and health economic analyses.

Recombinant Adjuvanted Zoster Vaccine and Reduced Risk of Coronavirus Disease 2019 Diagnosis and Hospitalization in Older Adults.

BACKGROUND: Some vaccines elicit nonspecific immune responses that may protect against heterologous infections. We evaluated the association between recombinant adjuvanted zoster vaccine (RZV) and coronavirus disease 2019 (COVID-19) outcomes at Kaiser Permanente Southern California. METHODS: In a cohort design, adults aged ≥50 years who received ≥1 RZV dose before 1 March 2020 were matched 1:2 to unvaccinated individuals and followed until 31 December 2020. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for COVID-19 outcomes were estimated using Cox proportional hazards regression. In a test-negative design, cases had a positive severe acute respiratory syndrome coronavirus 2 test and controls had only negative tests, during 1 March-31 December 2020. Adjusted odds ratios (aORs) and 95% CIs for RZV receipt were estimated using logistic regression. RESULTS: In the cohort design, 149 244 RZV recipients were matched to 298 488 unvaccinated individuals. The aHRs for COVID-19 diagnosis and hospitalization were 0.84 (95% CI, .81-.87) and 0.68 (95% CI, .64-.74), respectively. In the test-negative design, 8.4% of 75 726 test-positive cases and 13.1% of 340 898 test-negative controls had received ≥1 RZV dose (aOR, 0.84 [95% CI, .81-.86]). CONCLUSIONS: RZV vaccination was associated with a 16% lower risk of COVID-19 diagnosis and 32% lower risk of hospitalization. Further study of vaccine-induced nonspecific immunity for potential attenuation of future pandemics is warranted.

Effectiveness of booster BCG vaccination in preventing Covid-19 infection.

The evidence that BCG (bacille Calmette-Guerin) vaccine may increase the ability of the immune system to fight off pathogens other than tuberculosis has been studied in the past. This nonspecific immunity gained our interest, especially after initial reports of less cases in countries with universal BCG vaccination. In hopes of possible protective immunity, all staff of the Emirates International Hospital (United Arab Emirates) were offered a booster BCG vaccine in early March 2020. All the hospital staff were then tested for Covid-19 infection by the end of June 2020. We divided the subjects into two groups: booster vaccinated versus unvaccinated. The rate of Covid-19 infection was compared between the groups. Criteria included all staff who were offered the vaccine. Seventy-one subjects received the booster vaccination. This group had zero cases of positive COVID 19 infection. Two hundred nine subjects did not receive the vaccination, with 18 positive PCR confirmed COVID 19 cases. The infection rate in the unvaccinated group was 8.6% versus zero in the booster vaccinated group (Fisher's exact test p-value = .004). Our findings demonstrated the potential effectiveness of the booster BCG vaccine, specifically the booster in preventing Covid-19 infections in an elevated-risk healthcare population.

Old vaccines for new infections: Exploiting innate immunity to control COVID-19 and prevent future pandemics.

The COVID-19 pandemic triggered an unparalleled pursuit of vaccines to induce specific adaptive immunity, based on virus-neutralizing antibodies and T cell responses. Although several vaccines have been developed just a year after SARS-CoV-2 emerged in late 2019, global deployment will take months or even years. Meanwhile, the virus continues to take a severe toll on human life and exact substantial economic costs. Innate immunity is fundamental to mammalian host defense capacity to combat infections. Innate immune responses, triggered by a family of pattern recognition receptors, induce interferons and other cytokines and activate both myeloid and lymphoid immune cells to provide protection against a wide range of pathogens. Epidemiological and biological evidence suggests that the live-attenuated vaccines (LAV) targeting tuberculosis, measles, and polio induce protective innate immunity by a newly described form of immunological memory termed "trained immunity." An LAV designed to induce adaptive immunity targeting a particular pathogen may also induce innate immunity that mitigates other infectious diseases, including COVID-19, as well as future pandemic threats. Deployment of existing LAVs early in pandemics could complement the development of specific vaccines, bridging the protection gap until specific vaccines arrive. The broad protection induced by LAVs would not be compromised by potential antigenic drift (immune escape) that can render viruses resistant to specific vaccines. LAVs might offer an essential tool to "bend the pandemic curve," averting the exhaustion of public health resources and preventing needless deaths and may also have therapeutic benefits if used for postexposure prophylaxis of disease.

Are BCG-induced non-specific effects adequate to provide protection against COVID-19?

The world is experiencing a pandemic of Coronavirus Disease (COVID-19) caused by type-2 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). Vaccination is the only option to prevent future surges of the disease. Efforts for developing an effective vaccine are underway, but the timeline for the widespread availability of safe and effective vaccines is unknown. Some ecological reports have linked regional universal use of the Bacillus Calmette-Guerin (BCG) vaccine with reduced morbidity and mortality of COVID-19. BCG protects from non-tuberculous diseases through 'non-specific' effects mediated by the modulation of innate immunity. This commentary provides details of the immunological mechanism of BCG-induced 'trained innate immunity' responsible for its nonspecific protective effects. A probable role of the BCG vaccine in the current pandemic is also examined.