Since the first inoculation against smallpox by Edward Jenner in 1796, pioneers in this vaccine space continue to make strides at developing vaccines against endemic and pandemic infectious diseases for the betterment of public health. The impact of vaccines over the past couple of centuries has been recognized by leading organizations worldwide, including the World Health Organization (WHO) and the awarding of Nobel Prizes in Physiology or Medicine for the yellow fever vaccine in 1951 and discoveries leading to the development of effective mRNA vaccines against COVID-19 in 2023.
As a result of vaccination initiatives, diseases such as smallpox have been eradicated, with no cases occurring since 1977, and others are now limited to easily managed, local outbreaks. However, continued vigilance and ongoing vaccine development are needed to ensure appropriate responses are available for existing and emerging infectious diseases.
To celebrate our accomplishments, in this blog post, I provide a brief overview of the vaccine status for infectious diseases of interest in the United States. These include vaccines listed on the U.S. Centers for Disease Control and Prevention (CDC) vaccine schedule for children and recommended vaccines for adults.
Influenza
Influenza, or the flu, is widespread, seasonal, and varies from year to year. This creates challenges for effective vaccination, as we chase the most prevalent strains annually, but we have also had decades of experience. The first flu vaccine was licensed in 1945 for military use, after being developed with support from the US Army.
Soon after, in 1946, it was approved for civilian use and led to nationwide vaccination efforts. It was during the 1947 flu season that we found that existing vaccines were not effective for the prevalent viruses, and this led to the establishment of several WHO initiatives to track influenza strains globally, including the Global Influenza Surveillance and Response System (GISRS).
The flu vaccine is recommended for people of all ages. Although most flu vaccines are given via intramuscular injection, other modes of administration are available, including a nasal spray, and are under investigation in clinical trials. Finding more convenient methods is important to ensure greater coverage, especially considering the impact of flu on hospitalizations and death. In the U.S. between 2010 and 2023, the CDC estimates that the flu has resulted in 100,000-710,000 hospitalizations and 4,900-51,000 deaths annually.
Measles, MMR, and MMRV
Measles is one of the most contagious diseases experienced by humans. A single infected person can infect 90% of unvaccinated people with whom they come in close contact. Serious complications of the disease most often affect children younger than five years and adults older than 30 years.
Elimination (the absence of endemic transmission for ≥12 months) was made possible through nationwide vaccination after the first vaccine became available in 1963. Although measles was finally considered eliminated in the U.S. in 2000, under-vaccination in some areas of the country resulted in outbreaks in 2019. Since then, fewer than 400 cases have been reported in the U.S., and it is considered eliminated once again.
In the U.S., measles is included in the childhood vaccine schedule, in combination with mumps and rubella (MMR). This single shot against all three diseases was first made available in 1971.
The mumps vaccination program in the U.S. started in 1967 and resulted in a >99% decrease in mumps cases, although it can still occur, despite vaccination, when an infected person is in frequent close contact with others. Meanwhile, rubella incidence also decreased by >99% since its vaccine became available. It was officially considered eliminated in the U.S. in 2004, and fewer than 10 cases now occur annually.
Vaccination against the varicella-zoster virus (VZV), which causes varicella (commonly known as chickenpox), is also available in combination with the MMR (making it MMRV) vaccine. This version was approved in 2005 in the United States, following the approval of just the varicella vaccine in 1995. Most people who are vaccinated against VZV are protected for life and will not get varicella. Prior to vaccine availability, most people in the U.S. would get varicella by the time they were adults, with most cases occurring in children 15 years and younger. Since the first vaccine approval, the incidence has decreased by 97%.
Herpes zoster (shingles)
Herpes zoster (shingles) affects 30% of adults in the U.S. who had varicella previously — it is caused when VZV is reactivated. It results in a rash and can cause severe pain in the area of the shingles rash (known as postherpetic neuralgia). The CDC recommends herpes zoster vaccination for adults 50 years and older. As the VZV-vaccinated population increases (and therefore cases of varicella decrease), the incidence of shingles within that population is also expected to decrease.
Meningococcus
Although meningococcal disease can affect all ages, rates of infection are the highest in children younger than 1 year old, followed by those aged 16 to 23 years. U.S. cases spiked recently to 438 confirmed and probable cases in 2023, reaching the highest number since 2013. Although meningitis vaccines are on schedule for children and adolescents, low disease awareness can lead to poor vaccination rates. For example, only ~31% of U.S. adolescents have received a meningococcus B vaccine, and <12% have received both required doses.
The need to be vaccinated twice to cover all meningococcal disease groups (one vaccine for A, C, W, and Y and one vaccine for B) could also affect compliance with the vaccine schedule. Recently a couple of different vaccines combining all five groups in a single shot became available, which could improve vaccination rates and protection against invasive meningococcal disease (IMD). Although rare, IMD is a serious illness that can result in long-term consequences such as brain damage or amputations, life-threatening complications or death, primarily in children and adolescents.
Polio infection
Polio is well known for how much fear it spread through the population when it was prevalent. It is highly infectious, mostly affects young children, and can lead to spinal and respiratory paralysis and even death. There is no cure and no specific treatment for paralytic polio, adding to its severe impact.
Although polio has existed for as long as humans have been around, it wasn’t until 1949 that a breakthrough occurred on the path to a vaccine. Poliovirus was successfully cultivated in human tissue, and this work was awarded the 1954 Nobel Prize in Physiology or Medicine. The first inactivated polio vaccine (IPV) was licensed in 1955, resulting in a drop in annual cases from 58,000 to 5,600 in 1957 and 161 cases in 1961.
IPV is on the vaccine schedule for children, and as a result of vaccination, wild-type polio was eliminated from the U.S. in 1979. However, public health officials remain vigilant because cases can still occur, and travelers to the U.S. from countries where polio still exists can infect others.
Respiratory syncytial virus (RSV)
Another seasonal disease similar to influenza, RSV has resulted in 58,000-80,000 hospitalizations among children younger than five years and 100,000-160,000 hospitalizations among adults 60 years and older each year in the U.S. It can particularly cause severe illness in adults 75 years and older, who account for nearly half of all RSV-related hospitalizations and one-third of ICU admissions.
Therefore, the approvals of the first RSV vaccines in 2023 and another in 2024 were an exciting development to reduce the RSV-related burden, and it will be interesting to see the effect of these vaccines on the rates of illness and hospitalizations. The vaccines are available for older adults (≥60 years), adults aged 18 to 59 years at high risk of RSV-related complications, and pregnant women, which can provide vaccination benefits for their infant after birth.
Although RSV vaccination is on the schedule for children, no vaccine has yet been approved. Instead, they are administered an RSV antibody. However, RSV vaccines are being investigated for children. Overall, there are more than 15 RSV vaccines in clinical trials, which could help address the “tripledemic” of RSV, flu, and COVID-19.
Diphtheria, tetanus, and pertussis (DTaP)
Another combination vaccine on the vaccine schedule for children, DTaP protects against diphtheria, tetanus, and pertussis (whooping cough). Although diphtheria and tetanus are now uncommon in the U.S., pertussis continues to occur at rates of 10,000 cases each year. Because immunity wanes for all three diseases, boosters are recommended throughout adolescence and adulthood. In fact, the sporadic cases of tetanus that continue to occur in adults are typically the result of either not being vaccinated or not staying up to date with the 10-year booster shots.
Haemophilus influenzae type b (Hib)
The scientists working on a vaccine against diseases caused by Haemophilus influenzae type b (Hib) started in 1968, and it was first licensed in 1985, demonstrating how long it can take to successfully develop a safe, effective vaccine. It was a monumental accomplishment, however, given that Hib was the leading cause of bacterial meningitis and other invasive bacterial diseases among young children before vaccination was available. Children younger than 18 months accounted for approximately two-thirds, or 20,000, cases annually. After the vaccine was introduced, it was added to the children’s vaccine schedule, and the incidence of Hib has declined by 99%.
Hepatitis A and B
Vaccines against hepatitis A and B are on the childhood schedule, and the best way to prevent both is through vaccination. Because most infections occur in adults, the CDC has also recommended all people 19 to 59 years old to receive a hepatitis B vaccine regardless of the presence of risk factors. Both viruses infect the liver, and although hepatitis B can progress to a chronic infection potentially causing cirrhosis, liver cancer, and death, hepatitis A is self-limiting and does not become a chronic condition. However, there have been outbreaks of hepatitis A in multiple states among adults, with some cases serious enough to require hospitalization.
Human papillomavirus (HPV)
HPV infections are extremely common, and nearly everyone will have HPV in their lifetime. Although many of the HPV strains cause minimal symptoms, more than 42 million people in the U.S. become infected with high-risk strains that can cause other medical conditions. The role of these high-risk HPV strains in cervical cancer and other medical conditions was described in the 1990s, and this prompted the development of an HPV vaccine that could protect against cervical cancer. First approval for the vaccine occurred in 2006, and the CDC now recommends HPV vaccination starting at the age of 11 or 12 years. However, the vaccination series can be started as early as 9 years.
Pneumococci
Pneumococci continue to cause more than 50% of bacterial meningitis cases and 150,000 hospitalizations annually for pneumococcal pneumonia in the U.S. For children younger than five years, it is the most frequent bacterial cause of pneumonia, and it causes 10-30% of pneumonia cases in adults. Multiple vaccines are available in the U.S., each protecting against a different number of strains: 13, 15, 20, 21, and 23. The childhood vaccine schedule recommends the 15- and 20-strain pneumococcal vaccines, and diligent vaccination is needed to limit ongoing pneumococcal infections and hospitalizations.
Rotavirus
Prior to a vaccine becoming available, rotavirus was the most frequent cause of severe gastroenteritis in the United States, primarily for children younger than 5 years. At least one rotavirus infection was experienced by 95% of this population, and there were an estimated 2.7 million cases annually.
Although a vaccine was approved in the U.S. in 1998, it was removed from the market the next year due to safety concerns. It wasn’t until 2006 that the next generation of vaccines was approved. Now part of the CDC’s vaccine schedule for children, rotavirus vaccination is estimated to have prevented 62,000 emergency department visits and 45,000 hospitalizations every year.
SARS-CoV-19
The development of vaccines against SARS-CoV-19 during the COVID-19 pandemic demonstrated the speed at which they can be brought to market in the midst of a public health emergency. In addition, innovative vaccine technology in the form of mRNA vaccines was introduced, paving the way for this platform to be the foundation of future vaccines, such as RSV and cancer vaccines.
With the risk of seasonal COVID-19 infections and the tripledemic with RSV and influenza, COVID-19 vaccines are also now part of the childhood vaccine schedule and recommended for adults.
Mpox
Although not on the list of recommended vaccines, several outbreaks of mpox in the U.S. over the last couple of years highlights the risk of infectious diseases for high-risk individuals. A combination smallpox and mpox vaccine was approved by the FDA in 2019 and has been instrumental in containing and controlling the recent outbreaks.
Dengue
Recent cases of locally acquired dengue, which is transmitted by Aedes mosquitoes, were confirmed in California, Florida, Hawaii, Arizona, and Texas. Dengue is the most common mosquito-borne disease worldwide, but most cases in the U.S. were historically travelers to endemic countries. Detecting locally acquired cases increases the risk that it could become endemic in the U.S., increasing the risk of severe illness, which can involve internal bleeding, shock, and organ failure. The U.S. has an approved dengue vaccine, which could be more widely used if dengue cases continue to rise.
Other approved vaccines
As a result of worldwide initiatives to control prevalent infectious diseases, a number of other vaccines are currently available in the U.S. for tuberculosis, chikungunya, cholera, Ebola, Japanese encephalitis, and yellow fever. Many of these diseases are highly prevalent in other countries, and vaccination can play an important role in the prevention of disease for U.S. travelers visiting these countries — not only for the traveler but also for others they with whom they come in contact while traveling and after returning home.
Innovations in vaccines
As the list of diseases in this post shows, we have made great strides in preventing diseases for a large swath of our population. Still, there are other diseases with poor outcomes that would benefit from a vaccine. HIV is a great example of this. Although we have not yet produced a vaccine against HIV, ongoing work by scientists globally has moved us forward in this space. Other research is investigating new ways of administering vaccines that might be less burdensome and increase immunization rates, such as nasal sprays, patches, or orally. At the same time, different vaccine platforms, like mRNA, could offer better delivery, improved efficacy, and potentially fewer side effects.
Vaccines have changed the landscape of public health and saved lives worldwide. It’s exciting to be involved in groundbreaking research that contributes to the vaccines of the future. Feel free to contact me to discuss the vaccine research Headlands Research has been involved in and our capabilities that could support your next vaccine trial.
About the Author
With over 30 years of experience in clinical site operations, Michelle is a seasoned professional in the field of clinical research, known for a robust background in vaccine trials and expertise in multi-therapeutic areas. Throughout a distinguished career, she has contributed to over 500 clinical trials, with more than 200 specifically focused on vaccines, demonstrating a profound commitment to advancing medical research and public health.
Currently serving as the Director of Vaccine Strategy for Headlands Research Network, Michelle plays a pivotal role in developing and implementing strategic initiatives to enhance vaccine trial efficiency and efficacy. With a track record of excellence, she is dedicated to ensuring compliance with regulatory standards, optimizing study start-up processes, and maintaining high retention rates across all vaccine trials.
Michelle’s leadership and innovative approach have been instrumental in driving Headlands Research network’s mission to deliver high-quality data and bring safe, effective vaccines to market.