Session Highlights Opportunities and Challenges in Vaccine Development

Current vaccine development builds upon hundreds of years of scientific history, noted a featured speaker who highlighted vaccines in the pipeline for targeted diseases and specific populations during a session of the ATS 2021 International Conference.

Kristen Feemster, MD, MPH, MSHP, an adjunct associate professor of pediatrics at the University of Pennsylvania Perelman School of Medicine as well as the research director of the Vaccine Education Center at the Children's Hospital of Philadelphia, also spoke about implementation challenges and vaccine hesitancy.

There are more than 600 vaccines in development for a wide range of indications, including therapeutic ones, using 6 emerging vaccine platforms, said Feemster, who is also the global director of medical and scientific affairs of vaccines and infectious diseases at Merck.

Two of the 6 are messenger RNA (mRNA) or viral RNA vectors and DNA or viral DNA vector vaccines; the other 4 are peptide based; tumor antigens, or whole human cells; autologous vaccines; and recombinant polypeptides II.

The first part of her talk highlighted vaccines targeting diseases that cause severe illness or even death in infants but might be prevented through immunizing the mother.

“These are some of the first vaccines specifically being developed to protect infants through maternal immunization,” she said.

Currently, vaccination for influenza is recommended for pregnant women, as the risk of severe flu is higher in this population. Tetanus, diphtheria, and acellular pertussis (Tdap) are also recommended, as each carries a risk for young infants who are too young to receive vaccines.

In the pipeline are 2 vaccines that target morbidity and mortality in young infants, including Group B streptococcus (GBS) and respiratory syncytial virus (RSV).

GBS is a very common colonizer of the gastrointestinal and genitourinary tract, affecting about 50% of healthy adults, and it can be passed to infants during delivery. The current intervention—testing women for colonization and administering antibiotics at delivery if positive—is only effective for early and not late-onset disease.

RSV is a major cause of pneumonia and bronchiolitis in infants; the virus is very good at evading detection. While an antibody product is available for high-risk infants, it has limited availability.

GBS

Reviewing GBS vaccines under development, Feemster noted that group B strep, like pneumococcus, “is an encapsulated organism, so it has a polysaccharide capsule, and that is the primary virulence factor.”

The current candidates are largely conjugate vaccines:

• A trivalent conjugate vaccine targets 3 of the 10 serotypes known to cause illness: sereotypes Ia, IIb and III
• A hexavalent vaccine that covers more serotypes
• A protein-based vaccine, that, instead of focusing on the capsule, targets surface protein and might provide broader protection

The challenges with these vaccines include the feasibility of large-scale clinical efficacy trials, as well as defining protective antibody levels for an infant, she said.

RSV

An early effort to prevent RSV in the 1960s involved an inactivated vaccine, but it turned out to worsen illness in seronegative infants if they were exposed later, Feemster said.

Newer vaccines include a recombinant nanoparticle vaccine that targets the post-fusion F protein; it appears to be immunogenic with maternal antibody transfer in phase 2 trials, but efficacy has not been shown in phase 3 trials in infants.

Another is a monoclonal antibody against the F protein, which appears to be more than 70% effective when given to infants.

A third is a live attenuated virus vaccine that could be given intranasally.

Feemster also reviewed vaccine safety monitoring in pregnancy. These include both active and passive systems: the Vaccine Adverse Event Reporting System; pregnancy registries maintained by manufacturers; and active surveillance through the Vaccine Safety Data Link.

There is also the Vaccines and Medications in Pregnancy Surveillance System (VAMPSS), which uses perspective and case control surveillance to study the safety of exposures to vaccines and medications during pregnancy. She noted that in 2015, the National Vaccine Injury Compensation Program was expanded to include vaccines recommended for routine administration to pregnant women. The no-fault system, paid for by an excise tax on vaccines, was created in 1986 to provide a way for people who experienced a vaccine-related adverse event to be compensated. It does not cover every vaccine; instead, it covers vaccines that are routinely recommended for children.

Without the 2015 change, it would not have covered vaccines developed only for pregnant women.

Therapeutic vaccines

Therapeutic vaccines (for example, in oncology), target pathogenic proteins (or pathogenic T-cells), such as by slowing or stopping cancer cell growth, causing tumor cell death, or inhibiting pathogenic T cells in autoimmune diseases.

“So there's a lot of promise here, certainly, but there’s some challenges,” Feemster said, citing the similarity between tumor-specific proteins and normal cell proteins; the ability of tumor-specific proteins to evade immune response; and in autoimmune conditions, the risk of developing tolerance to self-antigens.

Therapeutic vaccines have utilized some of the newer vaccine platforms, she said, including recombinant polypeptides, oncolytic virus, peptide/protein vaccines, nucleic acid vaccines, and autologous vaccines.

There are 3 FDA-approved cancer vaccines (for metastatic prostate cancer, early-stage bladder cancer and metastatic melanoma),

Vaccine candidates for breast, kidney, lung, and other cancers are under review and are in phase 2 and phase 3 trials.

Other vaccine candidates using an antigen platform are targeting Alzheimer, type 1 diabetes, multiple sclerosis, addictions to cocaine and nicotine, and allergens like ragweed.

Implementation and hesitancy

As seen with the rollout of the 3 vaccines for COVID-19 this year, once a vaccine is developed, it is only as good as long as it is stored and handled correctly, and that it actually is put into use.

Some ideas being considered to make storage and administration easier include adjuvants to decrease the number of needed doses; increasing thermostability; using environmentally friendly packaging; or creating easier methods or devices for on-site reconstitution.

New delivery methods in the future could include dissolving needles; jet injection; microarray patches; oral sublingual administration; and more.

Feemster noted that reluctance to take new vaccines has been an issue since the launch of smallpox vaccines.

"Vaccine hesitancy is really multifactorial, related to competence and trust," she said. The scientific and health care community will need to continue to work to overcome misinformation, remembering that communicating the safety of vaccines and why it is important for public health can target complacency and build confidence.