Vaccine efficacy

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Influenza Vaccine

Vaccine efficacy or vaccine effectiveness is the percentage reduction of disease cases in a vaccinated group of people compared to an unvaccinated group. For example, a vaccine efficacy or effectiveness of 80% indicates an 80% decrease in the number of disease cases among a group of vaccinated people compared to a group in which nobody was vaccinated. When a study is carried out using the most favorable, ideal or perfectly controlled conditions, [1] such as those in a clinical trial, the term vaccine efficacy is used. [2] On the other hand, when a study is carried out to show how well a vaccine works when they are used in a bigger, typical population under less-than-perfectly controlled conditions, the term vaccine effectiveness is used. [1] [2]

Contents

Vaccine efficacy was designed and calculated by Greenwood and Yule in 1915 for the cholera and typhoid vaccines. It is best measured using double-blind, randomized, clinical controlled trials, such that it is studied under "best case scenarios." [3]

Vaccine efficacy studies are used to measure several important and critical outcomes of interest such as disease attack rates, hospitalizations due to the disease, deaths due to the disease, asymptomatic infection, serious adverse events due to vaccination, vaccine reactogenicity, and cost effectiveness of the vaccine. Vaccine efficacy is calculated on a set population (and therefore is not a constant value when counting in other populations), and may be misappropriated to be how efficacious a vaccine is in all populations.

Testing

Vaccine efficacy differs from vaccine effectiveness in the same way that an explanatory clinical trial differs from an intention-to-treat trial [ clarification needed ]: vaccine efficacy shows how effective a vaccine could be given ideal circumstances and 100% vaccine uptake (such as the conditions within a controlled clinical trial); vaccine effectiveness measures how well a vaccine performs when it is used in routine circumstances in the community. [4] What makes vaccine efficacy relevant is that it shows the disease attack rates as well as a tracking of vaccination status.[ jargon ] [4] Vaccine effectiveness is relatively inexpensive to measure than vaccine efficacy. The measurement of vaccine effectiveness relies on observational studies which are usually easier to perform, whereas a vaccine efficacy measurement requires randomized controlled trials which are time and capital intensive. [5] [4] Because a clinical trial is based on people who are taking the vaccine and those who are not, there is a risk for disease, and optimal treatment is needed for those who become infected.

The advantages of measuring vaccine efficacy is having the ability to control for selection bias, as well as prospective, active monitoring for disease attack rates, and careful tracking of vaccination status for a study population there is normally a subset as well; laboratory confirmation of the infectious outcome of interest and a sampling of vaccine immunogenicity. [4] [ failed verification ] The major disadvantages of vaccine efficacy trials are the complexity and expense of performing them, especially for relatively uncommon infectious outcomes of diseases for which the sample size required is driven up to achieve clinically useful statistical power. [4] Vaccine effectiveness estimates obtained from observational studies are usually subject to selection bias. [6] Since 2014, epidemiologists have used quasi-experimental designs to obtain unbiased estimates of vaccine effectiveness. [7] [8] [9]

Standardized statements of efficacy may be parametrically expanded to include multiple categories of efficacy in a table format. While conventional efficacy/effectiveness data typically shows the ability to prevent a symptomatic infection, this expanded approach could include prevention of outcomes categorized to include symptom class, viral damage minor/serious, hospital admission, ICU admission, death, various viral shedding levels, etc. Capturing effectiveness at preventing each of these "outcome categories" is typically part of any study and could be provided in a table with clear definitions instead of being inconsistently presented in study discussion as is typically done in past practice. [10]

Biological factors

Biological exposures such as parasites affect the immune responses after vaccination. [11] This can be seen in areas with a high burden of parasitic infections where vaccine responses are low for vaccines such as BCG. [12] Infections like malaria suppress immune responses to polysaccharide vaccines. A potential solution is to give curative treatment before vaccination in areas where malaria is present. [11] The effect of parasites on vaccine response has also been observed in individuals infected by helminths in areas that have a high burden of infectious diseases. Established helminth infections at the time of vaccination affect vaccine responses. [13]

Other biological factors such as smoking, age, sex, and nutrition also affect vaccine responses. In the case of hepatitis B vaccine, for example, increasing age, being male, having a body mass index > 25, and smoking can result in lower seroprotection rates. [14] In addition, other factors such as the composition of the gut microbiota can affect responses to vaccination. [15]

Formula

The outcome data (vaccine efficacy) generally are expressed as a proportionate reduction in disease attack rate (AR) between the unvaccinated (ARU) and vaccinated (ARV), or can be calculated from the relative risk (RR) of disease among the vaccinated group. [16] [17] [18]

The basic formula [19] is written as:with

An alternative, equivalent formulation of vaccine efficacy is: where is the relative risk of developing the disease for vaccinated people compared to unvaccinated people.

The design of clinical trials ensures that regulatory approval is issued only for effective vaccines. However, during research, it is possible that an intervention actually increases the risk of participants, for example, in the STEP and Phambili studies, which were both intended to test an experimental HIV vaccine . [20] In these cases, the formula would yield a negative efficacy value because . A negative efficacy value is sometimes present in the lower limit of a confidence interval of an estimate of vaccine efficacy for specific clinical endpoints. While this means that the intervention may actually have a negative effect, it could also be simply due to small sample size or sample variability.

Relative risk

First, the baseline risk can be calculated for each group and then vaccine efficacy (RRR) as follows:

Then,

Also, the absolute risk reduction (ARR) for any vaccine can simply be obtained from calculating the difference of risks between the groups i.e. 0.86%–0.196% which renders a value of about 0.66% for the above example.

Cases studied

The New England Journal of Medicine did a study on the efficacy of a vaccine for the influenza A virus. A total of 1,952 subjects were enrolled and received study vaccines in the fall of 2007. Influenza activity occurred from January through April 2008, with the circulation of influenza types:

Absolute efficacy against both types of influenza, as measured by isolating the virus in culture, identifying it on real-time polymerase-chain-reaction assay, or both, was 68% (95% confidence interval [CI], 46 to 81) for the inactivated vaccine and 36% (95% CI, 0 to 59) for the live attenuated vaccine. In terms of relative efficacy, there was a 50% (95% CI, 20 to 69) reduction in laboratory-confirmed influenza among subjects who received inactivated vaccine as compared with those given live attenuated vaccine. Subjects were healthy adults. The efficacy against the influenza A virus was 72% and for the inactivated was 29% with a relative efficacy of 60%. [21] The influenza vaccine is not 100% efficacious in preventing disease, but it is close to 100% safe, and much safer than the disease. [22] [23]

Since 2004, clinical trials testing the efficacy of the influenza vaccine have been slowly coming in: 2,058 people were vaccinated in October and November 2005. Influenza activity was prolonged but of low intensity; type A (H3N2) was the virus that was generally spreading around the population, which was very like the vaccine itself. The efficacy of the inactivated vaccine was 16% (95% confidence interval [CI], -171% to 70%) for the virus identification end point (virus isolation in cell culture or identification through polymerase chain reaction) and 54% (95% CI, 4%–77%) for the primary end point (virus isolation or increase in serum antibody titer). The absolute efficacies of the live attenuated vaccine for these end points were 8% (95% CI, -194% to 67%) and 43% (95% CI, -15% to 71%). [24]

With serologic end points included, efficacy was demonstrated for the inactivated vaccine in a year with low influenza attack rates. Influenza vaccines are effective in reducing cases of influenza, especially when the content predicts accurately circulating types and circulation is high. However, they are less effective in reducing cases of influenza-like illness and have a modest impact on working days lost. There is insufficient evidence to assess their impact on complications.

Related Research Articles

<span class="mw-page-title-main">Vaccine</span> Pathogen-derived preparation that provides acquired immunity to an infectious disease

A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and recognize further and destroy any of the microorganisms associated with that agent that it may encounter in the future.

<span class="mw-page-title-main">Herd immunity</span> Concept in epidemiology

Herd immunity is a form of indirect protection that applies only to contagious diseases. It occurs when a sufficient percentage of a population has become immune to an infection, whether through previous infections or vaccination, that the communicable pathogen cannot maintain itself in the population, its low incidence thereby reducing the likelihood of infection for individuals who lack immunity.

<span class="mw-page-title-main">Basic reproduction number</span> Metric in epidemiology

In epidemiology, the basic reproduction number, or basic reproductive number, denoted , of an infection is the expected number of cases directly generated by one case in a population where all individuals are susceptible to infection. The definition assumes that no other individuals are infected or immunized. Some definitions, such as that of the Australian Department of Health, add the absence of "any deliberate intervention in disease transmission". The basic reproduction number is not necessarily the same as the effective reproduction number , which is the number of cases generated in the current state of a population, which does not have to be the uninfected state. is a dimensionless number and not a time rate, which would have units of time−1, or units of time like doubling time.

<span class="mw-page-title-main">Influenza vaccine</span> Vaccine against influenza

Influenza vaccines, colloquially known as flu shots or the flu jab, are vaccines that protect against infection by influenza viruses. New versions of the vaccines are developed twice a year, as the influenza virus rapidly changes. While their effectiveness varies from year to year, most provide modest to high protection against influenza. Vaccination against influenza began in the 1930s, with large-scale availability in the United States beginning in 1945.

<span class="mw-page-title-main">Kennel cough</span> Upper respiratory infection affecting dogs

Kennel cough is an upper respiratory infection affecting dogs. There are multiple causative agents, the most common being the bacterium Bordetella bronchiseptica, followed by canine parainfluenza virus, and to a lesser extent canine coronavirus. It is highly contagious; however, adult dogs may display immunity to reinfection even under constant exposure. Kennel cough is so named because the infection can spread quickly among dogs in the close quarters of a kennel or animal shelter.

A breakthrough infection is a case of illness in which a vaccinated individual becomes infected with the illness, because the vaccine has failed to provide complete immunity against the pathogen. Breakthrough infections have been identified in individuals immunized against a variety of diseases including mumps, varicella (Chickenpox), influenza, and COVID-19. The characteristics of the breakthrough infection are dependent on the virus itself. Often, infection of the vaccinated individual results in milder symptoms and shorter duration than if the infection were contracted naturally.

Immunization during pregnancy is the administration of a vaccine to a pregnant individual. This may be done either to protect the individual from disease or to induce an antibody response, such that the antibodies cross the placenta and provide passive immunity to the infant after birth. In many countries, including the US, Canada, UK, Australia and New Zealand, vaccination against influenza, COVID-19 and whooping cough is routinely offered during pregnancy.

An attenuated vaccine is a vaccine created by reducing the virulence of a pathogen, but still keeping it viable. Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent. These vaccines contrast to those produced by "killing" the pathogen.

A subunit vaccine is a vaccine that contains purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response. Subunit vaccine can be made from dissembled viral particles in cell culture or recombinant DNA expression, in which case it is a recombinant subunit vaccine.

<span class="mw-page-title-main">Inactivated vaccine</span> Vaccine using a killed version of a disease pathogen

An inactivated vaccine is a vaccine consisting of virus particles, bacteria, or other pathogens that have been grown in culture and then killed to destroy disease-producing capacity. In contrast, live vaccines use pathogens that are still alive. Pathogens for inactivated vaccines are grown under controlled conditions and are killed as a means to reduce infectivity and thus prevent infection from the vaccine.

<span class="mw-page-title-main">Universal flu vaccine</span> Vaccine that prevents infection from all strains of the flu

A universal flu vaccine would be a flu vaccine effective against all human-adapted strains of influenza A and influenza B regardless of the virus sub type, or any antigenic drift or antigenic shift. Hence it should not require modification from year to year in order to keep up with changes in the influenza virus. As of 2024 no universal flu vaccine had been successfully developed, however several candidate vaccines were in development, with some undergoing early stage clinical trial.

Vaccine shedding is a form of viral shedding which can occasionally occur following a viral infection caused by an attenuated vaccine. Illness in others resulting from transmission through this type of viral shedding is rare. Most vaccines are not attenuated vaccines, and therefore cannot cause vaccine-induced viral shedding, though the idea of shedding is a popular anti-vaccination myth.

<span class="mw-page-title-main">Vaxart</span> American biotechnology company

Vaxart, Inc. is an American biotechnology company focused on the discovery, development, and commercialization of oral recombinant vaccines administered using temperature-stable tablets that can be stored and shipped without refrigeration, eliminating the need for needle injection. Its development programs for oral vaccine delivery include prophylactic, enteric-coated tablet vaccines for inhibiting norovirus, seasonal influenza, respiratory syncytial virus, and human papillomavirus. It was founded in 2004 by Sean Tucker. Originally incorporated as West Coast Biologicals, Inc. in California in 2004, the company later changed its name to Vaxart, Inc. in July 2007, after reincorporating in Delaware. A significant development in the company's history was the reverse merger with Aviragen Therapeutics, Inc. on February 13, 2018, which led to Vaxart becoming a wholly-owned subsidiary of Aviragen. Post-merger, the company continued as Vaxart, Inc.

<span class="mw-page-title-main">Arnold Monto</span> American physician and epidemiologist

Arnold Monto is an American physician and epidemiologist. At the University of Michigan School of Public Health, Monto is the Thomas Francis, Jr. Collegiate Professor Emeritus of Public Health, professor emeritus of both epidemiology and global public health, and co-director of the Michigan Center for Respiratory Virus Research & Response. His research focuses on the occurrence, prevention, and treatment of viral respiratory infections in industrialized and developing countries' populations.

<span class="mw-page-title-main">CoronaVac</span> Vaccine against COVID-19

CoronaVac, also known as the Sinovac COVID-19 vaccine, was a whole inactivated virus COVID-19 vaccine developed by the Chinese company Sinovac Biotech. It was phase III clinically trialled in Brazil, Chile, Indonesia, the Philippines, and Turkey and relies on traditional technology similar to other inactivated-virus COVID-19 vaccines, such as the Sinopharm BIBP vaccine, another Chinese vaccine, and Covaxin, an Indian vaccine. CoronaVac does not need to be frozen, and both the final product and the raw material for formulating CoronaVac can be transported refrigerated at 2–8 °C (36–46 °F), the temperatures at which flu vaccines are kept.

<span class="mw-page-title-main">Covaxin</span> Vaccine against COVID-19

Covaxin is a whole inactivated virus-based COVID-19 vaccine developed by Bharat Biotech in collaboration with the Indian Council of Medical Research - National Institute of Virology.

<span class="mw-page-title-main">Shabir Madhi</span> South African physician and professor

Shabir Ahmed Madhi, is a South African physician who is professor of vaccinology and director of the South African Medical Research Council Respiratory and Meningeal Pathogens Research Unit at the University of the Witwatersrand, and National Research Foundation/Department of Science and Technology Research Chair in Vaccine Preventable Diseases. In January 2021, he was appointed Dean of the Faculty of Health Sciences at the University of the Witwatersrand.

<span class="mw-page-title-main">Sputnik Light</span> Vaccine against COVID-19

Sputnik Light is a single dose COVID-19 vaccine developed by the Gamaleya Research Institute of Epidemiology and Microbiology. It consists of the first dose of the Sputnik V vaccine, which is based on the Ad26 vector, and it can be stored at a normal refrigerator temperature of 2–8 °C (36–46 °F). The institute says this version would be ideally suited for areas with acute outbreaks, allowing more people to be vaccinated quickly. It will also be used as a third (booster) dose for those who received Sputnik V at least 6 months earlier.

<span class="mw-page-title-main">COVID-19 vaccine clinical research</span> Clinical research to establish the characteristics of COVID-19 vaccines

COVID-19 vaccine clinical research uses clinical research to establish the characteristics of COVID-19 vaccines. These characteristics include efficacy, effectiveness, and safety. As of November 2022, 40 vaccines are authorized by at least one national regulatory authority for public use:

<span class="mw-page-title-main">Polyvalent influenza vaccine</span> Vaccine against multiple flu strains

Polyvalent influenza vaccine is a type of influenza vaccine that provides immunity against more than one type of antigen. In the second week after receiving the flu shot, the body's immune system is triggered by the antigens so the body starts producing antibodies. These antibodies help fight against influenza viruses. Influenza symptoms and deaths can be prevented by getting an influenza vaccine every year. Currently circulating influenza strains that can cause seasonal epidemics include influenza A viruses, which can be further divided into subtype A(H1N1) and A(H3N2), and influenza B viruses.

References

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