New Vaccines for 2021 and the Vaccine Development Pipeline

Vaccines and vaccine-preventable diseases have recently been thrust into the national spotlight due to the ongoing COVID-19 global pandemic. In the context of the pandemic, the vaccine approval process has received national scrutiny and has evoked an ongoing conversation about equity of distribution and access, optimal strategies for addressing vaccine hesitancy, and measures for combating health misinformation. The advancement of novel vaccine technologies and the ability to leverage experiences from COVID-19 to other potentially preventable communicable diseases has created opportunities to prevent diseases where vaccine development had previously not been possible. Beyond COVID-19, there have been several important updates related to the licensing and approval of vaccines against other communicable diseases from this past year that pharmacists should be aware of.

VACCINE DEVELOPMENT FOR PNEUMOCOCCAL DISEASE

According to the World Health Organization (WHO), lower respiratory tract infections, including pneumonia, represent the fourth leading cause of death around the world.¹ Pneumococcal disease, an acute bacterial infection caused by Streptococcus pneumoniae, or pneumococcus, can cause invasive disease—an infection of a normally sterile site—such as osteomyelitis, bacteremia without an infectious focus, pneumonia with bacteremia, septic arthritis, and meningitis—or noninvasive infections such as pneumonia without bacteremia, otitis media, and sinusitis.^2,3 In the United States, invasive pneumococcal infections have dramatically declined in both children and adults following the introduction of pneumococcal conjugate vaccines in 2000.⁴ Over a 20-year period (1998-2018), rates of invasive pneumococcal disease among children younger than 5 years decreased by 93%, a decline attributed to the efficacy of these vaccines.⁴

Pneumococcal disease may be difficult to distinguish from other communicable infectious diseases. Pneumococcal pneumonia may present as a secondary bacterial infection in someone who is also experiencing influenza.⁵ Influenza and COVID-19 are caused by viral pathogens and individuals with these infections may show no symptoms (be asymptomatic) to severe symptoms upon presentation. For COVID-19, it may take several days after exposure for an individual to present with symptoms (typically, an individual may experience symptoms approximately 5 days after being infected, but symptoms can appear 2 to 14 days after infection) whereas influenza symptoms usually appear 1 to 4 days after infection.⁶

According to the CDC, common symptoms that COVID-19 and influenza share include the following⁶:

• Fever or feeling feverish/having chills
• Cough
• Shortness of breath or difficulty breathing
• Fatigue (tiredness)
• Sore throat
• Runny or stuffy nose
• Muscle pain or body aches
• Headache
• Vomiting and diarrhea
• Change in or loss of taste or smell, although this is more frequent with COVID-19

For bacterial pneumonia, symptoms may include an abrupt onset of fever and chills, with repeated shaking chills or rigors being an uncommon finding. Other common symptoms may include pleuritic chest pain, productive cough, dyspnea, tachypnea, hypoxia, tachycardia, malaise, and weakness; gastrointestinal symptoms (nausea and/or vomiting) and headaches occur less frequently.²

Two new pneumococcal vaccines received FDA approval this year. In June and July 2021, the FDA approved the pneumococcal 20-valent conjugate vaccine, Prevnar 20 (Pfizer, Inc), and the pneumococcal 15-valent conjugate vaccine, Vaxneuvance (Merck & Co, Inc), both for adults 18 years or older.^7,8 It is important to note that the Prevnar 20 vaccine received approval under an accelerated approval process; additional confirmatory studies will be performed as a condition of the approval pathway. A summary of vaccine characteristics is included in the Table.^9,10

These 2 new pneumococcal vaccines join Prevnar 13 (PCV13; Pfizer Inc) and Pneumovax 23 (PPSV; Merck & Co, Inc) as FDA-approved pneumococcal vaccines available in the United States. According
to current immunization recommendations from the CDC Advisory Committee on Immunization Practices (ACIP), pneumococcal vaccination is recommended as part of the routine childhood immunization schedule for all children under 2 years and for all adults 65 years and older. Depending on the presence of other medical conditions or risk factors, individuals younger than 65 years also may need to receive pneumococcal vaccinations.^11,12

It is anticipated these new vaccines will be evaluated at the October 2021 meeting of the CDC’s ACIP for consideration for addition to the adult immunization guidelines; emerging data for use of the Vaxneuvance vaccine in children may additionally be forthcoming. There is an opportunity for pharmacists to provide education and recommend these vaccines accordingly with the emergence of further guidance.

OTHER RECENT VACCINE APPROVALS AND EXPANDED INDICATIONS FOR USE

Vaxelis, the first 6-in-1 (hexavalent) combination vaccine approved as a 3-dose immunization series (a 0.5-mL intramuscular injection administered at 2, 4, and 6 months of age) first received FDA approval in 2018. This vaccine, developed jointly by Merck and Sanofi, is intended to be part of a routine pediatric immunization series in children 6 weeks through 4 years of age (before their fifth birthday) and contains diphtheria and tetanus toxoids, and acellular pertussis adsorbed (Dtap); inactivated poliovirus; Haemophilus influenzae type b conjugate, and hepatitis B recombinant. Although initially approved by the FDA in 2018, Vaxelis was authorized by the ACIP as a combination vaccine option in the CDC’s Recommended Child and Adolescent Immunization Schedule in February 2021.^12-14 This product became available in the United States in summer 2021.

In August 2021, the FDA approved Ticovac (Pfizer Inc), a vaccine indicated to prevent tick-borne encephalitis (TBE) in individuals 1 year and older.15,16 This vaccine is presently the only FDA-approved vaccine indicated for prevention of TBE for adults and children visiting or living in TBE-endemic areas.¹⁷ For primary vaccination, it is administered at a dose of 0.25 mL (for ages 1-15 years) or 0.5 mL for ages 16 years and older as a 3-dose series; an additional booster—a fourth dose—may be considered at least 3 years after completion of the primary immunization series if ongoing or re-exposure to the TBE virus is expected. Contraindications to receipt of Ticovac include a severe allergic reaction to any vaccine component.¹⁶ The ACIP is expected to discuss recommendations on the safe and appropriate use of this vaccine at an upcoming meeting.

VACCINE DEVELOPMENT PIPELINE AND CONCLUSIONS

There are numerous other novel vaccines under development and investigation around the world. According to the WHO, pipeline vaccine candidates are presently in various stages of development for HIV-1 (see “Using mRNA to Create the Elusive HIV Vaccine” on page 24), malaria, norovirus, tuberculosis, and other infectious diseases.¹⁸ It is undeniable the lessons learned and rapid evolution of the science of vaccine immunology, including the role of messenger RNA (mRNA) and other technologies that emerged because of COVID-19, will have lasting impacts on virology and the potential realization of vaccines for diseases not traditionally addressed by vaccination.

Mary Barna Bridgeman, PharmD, BCPS, BCGP, FASCP, is a clinical professor at Ernest Mario School of Pharmacy at Rutgers University in Piscataway, New Jersey, and an internal medicine clinical pharmacist at Robert Wood Johnson University Hospital, also in New Jersey.

REFERENCES

1. World Health Association. Global health estimates: life expectancy and leading causes of death and disability. Accessed September 24, 2021. https://www.who.int/data/gho/data/themes/ mortality-and-global-health-estimates
2. Gierke R, Wodi AP, Kobayashi M. Pneumococcal disease. CDC. August 18, 2021. Accessed September 24, 2021. https://www.cdc.gov/vaccines/pubs/pinkbook/pneumo.html
3. Pneumococcal disease: types of infection. CDC. September 1, 2020. Accessed September 24, 2021. https://www.cdc.gov/ pneumococcal/about/infection-types.html
4. Pneumococcal disease: surveillance and reporting. CDC. September 1, 2020. Accessed September 24, 2021. https://www.cdc.gov/pneumococcal/surveillance.html
5. Morris DE, Clearly DW, Clarke SC. Secondary bacterial infections associated with influenza pandemics. Front Microbiol. 2017;8:1041. doi:10.3389/fmicb.2017.01041
6. Similarities and differences between flu and COVID-19. CDC. June 7, 2021. Accessed September 24, 2021. https://www.cdc.gov/ flu/symptoms/flu-vs-covid19.htm
7. BLA approval and BLA accelerated approval for the pneumococcal 20-valent conjugate vaccine. FDA. June 10, 2021. Accessed September 27, 2021. https://www.fda.gov/media/ 150021/download
8. BLA approval for the pneumococcal 15-valent conjugate vaccine. FDA. July 16, 2021. Accessed September 27, 2021. https://www.fda.gov/media/150820/download
9. Prevnar. Prescribing information. Pfizer Inc; 2021. Accessed September 24, 2021. http://labeling.pfizer.com/ShowLabeling. aspx?id=15428
10. Vaxneuvance. Prescribing information. Merck & Co Inc; 2021. Accessed September 24, 2021. https://www.fda.gov/ media/150819/download
11. Recommended adult immunization schedule for ages 19 and older, United States, 2021. CDC. February 11, 2021. Accessed September 24, 2021. https://www.cdc.gov/vaccines/schedules/ downloads/adult/adult-combined-schedule.pdf
12. Recommended child and adolescent immunization schedule for ages 18 years or younger, United States, 2021. February 11, 2021. Accessed September 24, 2021. https://www.cdc.gov/vaccines/ schedules/downloads/child/0-18yrs-child-combined-schedule.pdf
13. Vaxelis. FDA. October 29, 2020. Accessed September 24, 2021. https://www.fda.gov/vaccines-blood-biologics/vaxelis
14. Vaxelis. Prescribing information. Merck & Co; 2020. Accessed September 24, 2021. https://www.fda.gov/media/ 119465/download
15. BLA approval for the tick-borne encephalitis vaccine. FDA. August 13, 2021. Accessed September 27, 2021. https://www.fda. gov/media/151516/download
16. Ticovac. Prescribing information. Pfizer Inc; 2021. Accessed September 24, 2021. https://www.fda.gov/media/151502/download
17. U.S. FDA approves Ticovac, Pfizer’s tick-borne encephalitis (TBE) vaccine. Pfizer. August 13, 2021. Accessed September 24, 2021. https://www.pfizer.com/news/press-release/ press-release-detail/us-fda-approves-ticovactm-pfizers-tick-borne-encephalitis
18. World Health Organization. Research and product development by disease. vaccine-preventable diseases (including pipeline vaccines). Accessed September 24, 2021. https:// www.who.int/teams/immunization-vaccines-and-biologicals/diseases