Russell Libby, MD, is an assistant clinical professor of pediatrics at the University of Virginia School of Medicine in Charlottesville, Virginia, and at the George Washington University School of Medicine in Washington, DC.

Russell Libby, MD

No aspect of pediatric medicine has been as impactful on the health and well-being of our patients and communities as the vaccines that now routinely prevent 16 diseases that were once commonplace.

 Current vaccines include those based on live attenuated viruses (eg, varicella, rotovirus), killed whole organism (eg, rabies, hepatitis A), polysaccharide or native proteins (eg, pneumococcal, meningococcal), and recombinant or whole molecular modification (eg, hepatitis B, herpes zoster).

Today nearly 260 vaccines are in development. Many of these are directed at infectious diseases, but many novel vaccines are being developed to treat or prevent allergies, autoimmune disorders, cancers, and even Alzheimer disease.

 Following the emergence of severe acute respiratory syndrome (SARS) in 2003 and Middle East respiratory syndrome (MERS) in 2012, both deadly coronavirus infections, investigators spent subsequent years developing and perfecting innovative vaccines including adenovirus vector vaccines and messenger RNA (mRNA) vaccines.

Both vaccine types were rapidly adapted to combat the SARS-CoV-2 pandemic once the Chinese published the genetic sequence of SARS-CoV-2 in January 2020.2 These vaccines instruct cells to manufacture specific antigens—ie, the spike proteins in the case of the SARS-CoV-2 virus—so that the immune system manufactures spike protein antibodies. As of this writing, the United States has deployed 2 mRNA vaccines (Pfizer and Moderna), as well as a genetically engineered adenovirus vector vaccine (Johnson & Johnson).

Both vaccine technologies can easily be modified to target a litany of other viruses. To date, several adenovirus vector vaccines for HIV, Ebola virus, influenza virus, Mycobacterium tuberculosis, and Plasmodium falciparum are under human clinical trials, and others are being developed against rabies, dengue virus, and MERS. Currently, mRNA-based vaccines are in development against HIV, rabies, Zika, cytomegalovirus, respiratory syncytial virus (RSV), Ebola, and others.

These vaccine technologies have also shown great promise against several types of cancer. More than 150 clinical trials assessing mRNA vaccines and more than 200 clinical trials involving adenovirus vector vaccines for infectious diseases and cancers are currently ongoing, according to ClinicalTrials.gov. It is even anticipated that a universal flu vaccine based on these technologies will be developed, and it will no longer require seasonal modifications because it will target stable antigens among influenza viruses. It is also predicted that there will be new vaccines based on virus like particles (VLPs).

These are artificial viruses made up of copies of 1 or more viral proteins that self-assemble into nanoparticles. Current VLP vaccines include the hepatitis B vaccine (Energix-B) and the human papillomavirus vaccine (Gardasil). VLP vaccines are also being developed for chikungunya, Japanese encephalitis, yellow fever, Zika, and malaria, among other diseases.

Yet another new type of vaccine— against allergic asthma—is being investigated. Allergic asthma is characterized by mucus secretion, airway eosinophilia, and elevated levels of IgE antibodies and increased levels of cytokines IL-3 and IL-4. Recently, researchers produced an experimental conjugate vaccine against these interleukins that in animal models have shown prolonged reduction of IgE levels, airway hyperresponsiveness, eosinophilia, and mucus production.

Additionally, there are new vaccine delivery systems under development. The most common method of immunizing children to date has been the direct injection of vaccines either intramuscularly or subcutaneously. Several years ago, a live attenuated influenza intranasal vaccine was developed, which has benefited countless needle-phobic children and adults.

Now Altimmune has developed an adenovirus-vectored intranasal vaccine, now in phase 1 clinical trials, that generates a broad IgG, mucosal IgA, and T-cell response to SARS-CoV-2 and is stable at room temperature.5 Altimmune is also in clinical trials for intranasal vaccines for anthrax and influenza.

Several companies are developing a microneedle patch to administer vaccines. The microneedles are impregnated with vaccine that targets immune cells in the dermis.6 Best of all, these are pain free and stable at room temperature. The patch is applied via a preloaded applicator and removed after a few minutes, leaving the vaccine-impregnated tips embedded in the dermis, releasing vaccine over time.

These patches are being investigated as a potential alternative to intramuscular vaccines for influenza and COVID-19. Two more vaccine delivery systems may change the way patients are immunized. An oral vaccine mechanism, Vector-Adjuvant-Antigen Standardized Technology (VAAST), which targets mucosal IgA, is being perfected by Vaxart. VAAST has shown promising results for H5N1 influenza, H1N1 influenza, influenza B, norovirus, and RSV.

The second is a vaccine capsule filled with nanoparticles, injected subcutaneously, that would slowly release the vaccine over time, potentially eliminating the need for immunization booster doses.7 Enesi Pharma is developing a universal vaccine implant (UVI) using their ImplaVax needle-free delivery device to inject each UVI up to 7 mm into the dermis (Figure 2). Preclinical studies have shown this method to be as effective as intramuscular or subcutaneous injections, with less pain associated with injection, according to the company.

Vaccine technologies in development may facilitate a rapid and effective response to new threats and likely will target not only infectious diseases but also allergies, autoimmune conditions, and cancers. Additionally, new vaccine delivery systems will overcome production and storage obstacles that have slowed the response to the COVID-19 pandemic. Pediatricians and parents, recognizing how much vaccines improve the health and well-being of young patients, have much to look forward to.

Articles

Vaccine technologies in development may facilitate a rapid and effective response to new threats and likely will target not only infectious diseases but also allergies, autoimmune conditions, and cancers. 

Vaccinology: New Vaccine Technology for Autoimmune, Cancers, Infectious Diseases

The first population-based vaccine registry in the United States launched in Delaware in 1974 and did not begin to flourish until the Robert Wood Johnson Foundation launched their All Kids Count program in 1991. Government funding for immunization registries became available when President Bill Clinton included immunization registries in his Childhood Immunization Initiative in 1993.

There are currently 63 registries, now called immunization information systems (IISs), in the United States. These include state-, island-, and city-based IISs, each operating independently under its respective local and state policies with their own rules around collection and use of data, analysis, and operational routines.

Figure 1 shows the percentage of children under 6 participating in a state-based IIS as of 2019.

An ISS is a confidential, population-based, computerized database that records all immunization doses administered by participating providers within a geographic area. IISs provide a consolidated record of administered vaccines for the benefit of the patient, their family, and the greater public health. An IIS keeps a record of vaccinations given, dates, and manufacturing details, and can identify when a future or missed vaccination should be given.

IISs have many advantages; they can improve immunization rates, reduce vaccination errors, identify opportunities to vaccinate, provide epidemiological insights when there is a community outbreak of a vaccine-preventable disease, and allow access by patients, families, schools, and other health care providers. 

An IIS can also reduce time spent entering data and track vaccine inventory, especially if it is connected through your electronic health record (EHR) system. An IIS can make a child’s immunization portable when the family changes practices, moves from one location to another, or seeks care outside the medical home.

The administering site is credentialed by the individual IIS under licensed providers who can designate access for data entry and/or viewing by staff. Access to view is allowed for the patient, parents, and specified agencies, such as schools, pharmacies, urgent care facilities, and hospitals. 

There are federal requirements for documenting vaccines established by the CDC, which includes the specific vaccine, manufacturer, lot number, the date and location, and that the patient and/or family was given a vaccine information statement (VIS) to review with its publication date.3 Most systems will identify when a dose of a specific vaccine should be given and have specific time intervals that are not forgiven when a sequential dose is given too early.

It is the responsibility of the administering site to enter the required data, and it can be a burden to staff when they need to enter the data in multiple locations, such as the registry, the EHR, and the patient vaccination card. Most pediatric-specific EHRs are certified and connect with a local IIS, requiring only 1 point of data entry that will be shared with the IIS, the medical record, and the patient copy.

There is significant evidence that IISs improve vaccination rates and reduce missed opportunities for administering immunizations. Australia implemented a national IIS in 1996 and demonstrated an increase in full immunization among 2-year-old children from 64% in 1997 to 93% in 2007.4 Australia has a national health care system that facilitates implementation and utilization of IISs. Although the United States has yet to implement a national IIS, studies have repeatedly demonstrated that

IISs improve vaccination rates, reduce missed opportunities for vaccinations, and facilitate responses to community outbreaks of diseases.

The most significant problem with existing vaccine registries in the US is the lack of interoperability between them. Few nonpediatric-specific EHRs can currently extract data from local and state registries, or deposit immunization information directly into them. This necessitates office staff performing double entries of immunizations into the office EHR and the local IIS, which is time-consuming and unwieldly.

One method of speeding up data entry is the integration of barcode scanning into EHRs. After receiving a shipment of vaccine, the shipment form is scanned into a vaccine inventory, which is integrated into the EHR. When vaccines are ordered for a patient, the barcode on the vial is scanned again and screened by the connected IIS. 

Warnings appear if the vaccine is being given too soon, is not age appropriate, is attributed to the wrong funding source (eg, Vaccines for Children Program), or has expired. The staff manually enters the other vaccine administration details into the EHR and the information is electronically sent to the appropriate IIS. Over the next few years, it is anticipated that a growing number of EHRs will have this capability.

There is no uniform rule requiring an administering site to enter that data into the IIS, which further complicates the potential for interoperability. However, the COVID-19 pandemic and the CARES Act may be creating a new opportunity for data sharing between EHRs and the IISs. 

All sites administering COVID-19 vaccines must report all vaccinations into a database that allows for capturing the event and providing reminders for a second dose as indicated by the vaccine given. It may open the opportunity to connect all vaccine registries into a national database, accessible from anywhere.

Immunization Information Systems provide confidential, population-based, computerized database that records all immunization doses administered by participating providers within a geographic area. 