Immunization Update

Stephan L. Foster, PharmD, FAPhA

CDC’s Advisory Committee on Immunization Practices (ACIP) met in Atlanta on February 26–27, 2020, to discuss the current influenza season and vaccine effectiveness; coronavirus; Ebola, dengue, and rabies vaccines; and other immunization topics.

Influenza

Seqirus presented the results of a Phase III postmarketing trial of its adjuvanted quadrivalent influenza vaccine ([aIIV4] Fluad Quadrivalent) that evaluated its immunogenicity, efficacy, and safety. Vaccine efficacy (VE) against any polymerase chain reaction–confirmed influenza ranged from 19.8% to 51%. The secondary objective, VE against culture-confirmed influenza due to antigenically matched strains, did not achieve statistical significance. The study demonstrated a robust immune response against all four strains along with an expected and acceptable tolerability profile similar to that of aIIV3 (Fluad), the trivalent vaccine.

Influenza surveillance data presented by CDC showed that A(H1N1) strains, along with B/Victoria lineage strains, primarily circulated during the 2019–2020 season. The rate of influenza hospitalizations for adults was similar to that of most seasons, but rates in children and adolescents were higher. The rate of pediatric deaths is one of the highest in recent years. Of 105 pediatric deaths, 16% of the children were vaccinated, and 54% had no concurrent illness.

Interim estimates of 2019–2020 seasonal influenza vaccine effectiveness against medically attended influenza for any virus was 45%; against B/Victoria, 50%; and against A(H1N1), 37%, with differences seen in various age groups. 

A safety study comparing the adjuvanted versus high-dose inactivated vaccines in older adults showed that the number of participants with moderate to severe injection site pain was similar (3.2% for aIIV3, 5.8% for high dose). No serious adverse effects were observed with either vaccine, and either is an acceptable option for prevention of influenza in older adults.

2019 novel coronavirus (2019-nCov)

CDC has more than 800 personnel working on the coronavirus outbreak; for current information, visit www.cdc.gov/coronavirus/2019-ncov/index.html. The new strain has been labeled novel coronavirus (nCoV or COVID-19) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak of respiratory disease caused by the novel coronavirus was first detected in Wuhan City, Hubei Province, China. As of the date of the ACIP meeting, the disease had been detected in 37 locations internationally, with 15 cases in the United States. 

Coronaviruses are a large family of viruses that cause illness ranging from the common cold to more severe disease, as was seen in Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV). These viruses are common in many different species of animals, including camels, cattle, cats, and bats. The current outbreak is believed to have been transmitted from a bat to a human initially and is now spread through respiratory droplets between people who are in close contact (within 6 ft).

Early flu-like symptoms include fever, cough, and shortness of breath.  In more severe cases, pneumonia, SARS, kidney failure, cardiac failure, and death occur. CDC states that symptoms may appear between 2 to 14 days after exposure. There is no specific treatment (except supportive) or vaccine available currently, and a vaccine will likely take a year to develop.

Prevention through social distancing and sanitary habits are the only recommended actions. In general, CDC does not recommend wearing a face mask by members of the public as protection from any respiratory diseases, including COVID-19. Face masks should be used by people who show symptoms of COVID-19 to help prevent the spread of the disease and by health care workers and caregivers in close settings (at home or in a health care facility).

Ebola

The rVSVΔG-ZEBOV-GP (Ervebo—Merck) vaccine was FDA approved on December 19, 2019, for individuals ages 18 years and older. An outbreak of Ebola virus disease (EVD) in the Democratic Republic of Congo (DRC) was declared a Public Health Emergency of International Concern by the World Health Organization (WHO) in July 2019.

EVD can be caused by four different species in the genus Ebolavirus; the most common is Zaire ebolavirus. More than 31,000 cases and over 12,000 deaths have occurred due to EVD, with an untreated mortality rate of 70% to 90%. Within 1 year of discharge, survivors have a fivefold greater mortality rate than individuals in the general population. 

The latest outbreak in the DRC began on August 1, 2018. As of February 18, 2020, there were more than 3,000 cases with 2,000 deaths, and 165 health care workers had been infected. In the United States, 11 people had been treated for EVD, and of these patients, 2 had died.

The EVD vaccine is a recombinant vesicular stomatitis virus with glycoprotein substitution from the viral envelope of Zaire ebolavirus. Studies performed in monkeys showed 100% efficacy if the vaccine is given within 42 days of challenge. Rapidly initiated clinical studies across 10 countries demonstrated vaccine safety with only rare transient events that were mild to moderate. ACIP members discussed their concerns about reports of arthralgia and arthritis in some patients who received the vaccine.

Virus dissemination and replication occurred and persisted for 2 to 3 weeks following vaccination, though this vaccine cannot cause EVD infection. There are no known immune correlates of immunogenicity; antibodies develop beginning 14 days after vaccination and persist for at least 24 months.

The ACIP workgroup has identified three U.S. population groups at risk for exposure, including individuals responding to an outbreak, lab and support staff at biosafety level 4 facilities, and health care personnel at a federally designated Ebola treatment center who are involved in care and transport of patients. Other populations being discussed as at risk are personnel working at state-level Ebola treatment centers, Ebola assessment hospitals, and front-line hospitals.

Following presentations on GRADE (Grading of Recommendations, Assessment, Development and Evaluations) analyses, the workgroup recommended and ACIP voted to approve the following statement:

“Pre-exposure vaccination with rVSVΔG-ZEBOV-GP vaccine is recommended for adults 18 years of age or older in the U.S. population who are at potential risk for exposure to ebolavirus (species Zaire ebolavirus) and

• Are responding to an outbreak of EVD; or
• Work as health care personnel at a federally designated Ebola treatment center in the United States; or
• Work as laboratorians or other staff at biosafety level 4 facilities in the United States.”

Rabies

The rabies workgroup has been discussing pre-exposure prophylaxis (PrEP) since the last meeting. Two rabies vaccines are available: human diploid cell vaccine (Imovax—Sanofi Pasteur) and purified chick embryo cell vaccine (RabAvert—GlaxoSmithKline). Avoiding exposure, along with vaccinating domestic animals, is the most important intervention to prevent rabies. 

PrEP vaccination of humans is recommended for persons at higher risk, including those in select occupations or involved in activities such as spelunking or international travel. Postexposure prophylaxis, recommended for everyone who has been exposed, includes wound cleaning, vaccination, and possibly rabies immune globulin. Currently, the primary vaccine series alone is not a substitute for postexposure prophylaxis, and only I.M. administration of the vaccines is recommended.

The workgroup has been tasked with evaluating different schedules, a two-dose series, boosters, and frequency of titer checks. Initial results of a meta-analysis comparing a two-dose schedule (0 and 7 days) to the current three-dose schedule showed that the immunological response for the two schedules (two or three dose) is similar; however, titers fall rapidly during the first 6 months for both schedules. A booster dose appears to prolong duration, with a slow rate of decay.

Because these data are from small studies (<100 participants), many ACIP members were not comfortable changing the recommendations for a potentially fatal disease and will revisit the issue in future meetings.

Dengue

WHO lists dengue as one of the top 10 disease threats worldwide. Because dengue vaccine efficacy is high in patients who are seropositive (those with previous exposure) and much lower in patients who are seronegative, the vaccine is not recommended unless titers are performed to demonstrate previous infection. 

WHO recommends use of the vaccine if prevaccination screening can be performed. However, point-of-care laboratory tests, including rapid diagnostic tests, have not been validated and are not yet recommended. Based on available data over a 5-year period in the Philippines, the vaccine would avert 18 dengue hospitalizations in seropositive patients for each precipitated dengue hospitalization in seronegative patient vaccinated.

While dengue is a high public health priority, there are significant issues in vaccine implementation. A survey of the general population of Puerto Rico showed that 75% would receive the vaccine if it were free; this rate dropped to 59% for a $10 dose, 37% for a $20 dose, and 12% for a $50 dose. A survey of physicians reported only 39% administered vaccines in their offices. Most parents indicated they would agree to vaccination, and many physicians said they would administer the vaccine if they had more information or education.

Polio

Polio eradication is based on eliminating oral poliovirus type 1, which continues in Afghanistan and Pakistan (with 173 cases in 2019), and vaccine-derived poliovirus that can mutate to transmit, particularly in areas of low vaccine coverage. 

In 2016, oral poliovirus type 2 (OPV2) was removed from all routine vaccines, and a transition to withdraw all oral polio vaccines is under way. Since 2016, a large increase has occurred in type 2 vaccine-derived poliovirus (cVDPV) cases, and more than four rounds of vaccination may be required to stop some of these outbreaks. These increases may be caused by decreasing population mucosal immunity since OPV2 was withdrawn in 2016, and a modified OPV2 vaccine may be required in areas of outbreaks. Development of new vaccines is ongoing.

Hepatitis B

The hepatitis B workgroup is considering whether hepatitis B recommendations should continue to be risk based or changed to a universal recommendation.

General Best Practices updates

Updates to the General Best Practices Guideline for Immunization are ongoing and are posted on CDC’s website (www.cdc.gov/vaccines/ed/general-recs) as changes are made. Complete meeting minutes are at www.cdc.gov/vaccines/acip/index.html.