Skip directly to site content Skip directly to search


Español  Other Languages


Centers for Disease Control and Prevention. CDC twenty four seven. Saving Lives, Protecting People
 Search
		×
			Vaccines site
			Vaccines site
				All CDC
				Submit
			For a full list of topics:A-Z Index
			Advanced Search
		Advanced Search


Advisory Committee on Immunization Practices (ACIP)








ACIP Grading of Recommendations Assessment, Development and Evaluation (GRADE) for Booster Dose of Rabies Vaccine						Print
																Related Pages
										Introduction
In February and June 2021, a 2-dose rabies pre-exposure prophylaxis (PrEP) series was recommended for all persons for whom rabies PrEP is recommended. A one-time rabies antibody titer during years 1-3 (and a booster dose if the titer is <0.5 IU/mL) was recommended for persons at sustained risk for only recognized exposures (i.e., risk category 3 of the recommendations of the Advisory Committee on Immunization Practices [ACIP]). During February and June 2021, ACIP recommended a rabies vaccine booster dose as an alternative to the one-time titer check, no sooner than day 21 but no later than 3 years after the 2-dose PrEP series for those in risk category 3.
Methods
During September 2019–November 2021, the ACIP Rabies Work Group participated in monthly or bimonthly teleconferences and considered evidence-based updates to the 2008 ACIP recommendations. As a basis for the GRADE analysis, the policy question about an intramuscular booster dose of rabies vaccine (as an alternative to a titer check) was defined consisting of the population, intervention, comparison, and outcomes of interest (Table 1).  The Work Group designated primary immunogenicity a critical outcome (Table 2). Adverse events were not evaluated because the two rabies vaccines recommended in the United States (human diploid cell culture vaccine [HDCV] and purified chick embryo cell vaccine [PCECV]) have shown favorable safety profiles for decades and no new concerns have been identified. A systematic review of the evidence was conducted and observational data identified. A modified GRADE approach was taken where evidence certainty ranges from type 1 (high certainty) to type 4 (very low certainty) (www.cdc.gov/vaccines/acip/recs/index.html). Summary evidence for primary immunogenicity was determined and discussed.Table 1: Policy Question and PICO
Table 1: Policy Question and PICO
Policy question:
Should an IM booster dose of rabies vaccine (HDCV* or PCECV§) be recommended as an alternative to a titer check no sooner than day 21 and no later than 3 years after the 2-dose pre-exposure prophylaxis (PrEP) series IM [0, 7 days] for those in the #3 risk category of people who receive PrEP?Population
Persons in the #3 risk category for whom rabies vaccine PrEP is recommendedIntervention
Day 21 to year 3 rabies vaccine booster after [0, 7 days] rabies vaccine PrEP schedule with HDCV* or PCECV§Comparison
No rabies vaccine booster after [0, 7 days] rabies vaccine PrEP schedule with HDCV* or PCECV§Outcomes
Long-term immunogenicity*Human diploid cell culture vaccine§Purified chick embryo cell vaccineTable 2: Outcomes and Rankings
Table 2: Outcomes and Rankings
Outcome
Importance*
Included in evidence profileLong-term immunogenicity
Critical
Yes
*Three options: 1. Critical; 2. Important but not critical; 3. Not important for decision makingAppendix 1: Studies Included in the Review of Evidence
Appendix 1: Studies Included in the Review of Evidence
Last name first author, Publication year
Study design
Country (or more detail, if needed)
Age (measure central tendency – mean/SD; median/IQR; range)
Total population
N Intervention
N comparison
Outcomes
Funding sourceEndy, 2019
RCT
USA
Mean 32.4, Range 18 – 59
59
20
No comparison1
serologic immune response, adverse events
US Department of Defense, Defense Health Agency through the Medical Research and Development CommandSoentjens, 2019
RCT
Belgium
Median 29.0, NR
500
183
No comparison1
safety and immunogenicity
Institute of Tropical Medicine, Belgium1No comparison data available for this policy question available in these studies.Table 3a: Summary of Studies Reporting Outcome
Table 3a: Summary of Studies Reporting Outcome
Authors
last name, pub year
Age (years)
N intervention
N comparison
Vaccine
Absolute difference/effect estimate
Study limitations (Risk of Bias)Endy, 2019
Mean 32.4, Range 18 – 59
20
No comparison1
PCEC, IM
Not able to calculate2
8/9 Minimal concernsSoentjens, 2019
Median 29.0, NR
183
No comparison1
HDCV, IM
Not able to calculate2
8/9 Minimal concerns1No comparison data available for this policy question available in these studies.2No comparison data available to calculate effect estimate.3Study quality for observational studies was assessed using the Newcastle Ottawa Scale.Table 4: Grade Summary of Findings Table
Table 4: Grade Summary of Findings Table
Certainty assessment
Impact
Certainty
ImportanceNo of studies
Study design
Risk of bias
Inconsistency
Indirectness
Imprecision
Other considerations**Anamnestic response after booster (follow up: range 1 to 3 weeks)**2 1,2
observational studies
not serious
not serious
not serious
not serious
none
A historical control of trial participants receiving 2 doses of rabies vaccine resulting in 100% immunogenicity (n=264) at 1-3 weeks following vaccination schedule (Endy 2019, Soentjens 2019) : 410/410 (100%) seroconverstion with booster
Level 3
Low
CRITICALTable 5: Summary of Evidence for Outcomes of Interest
Table 5: Summary of Evidence for Outcomes of Interest
Outcome
Importance
Included in profile
CertaintyLong-term immunogenicity
Critical
Yes
Level 3, LowReferences
Endy, T. P., Keiser, P. B., Wang, D., Jarman, R. G., Cibula, D., Fang, H., Ware, L., Abbott, M., Thomas, S. J., Polhemus, M. E.. Serologic Response of 2 Versus 3 Doses and Intradermal Versus Intramuscular Administration of a Licensed Rabies Vaccine for Preexposure Prophylaxis. J Infect Dis; Apr 7 2020.
Soentjens, P., Andries, P., Aerssens, A., Tsoumanis, A., Ravinetto, R., Heuninckx, W., van Loen, H., Brochier, B., Van Gucht, S., Van Damme, P., Van Herrewege, Y., Bottieau, E.. Preexposure Intradermal Rabies Vaccination: A Noninferiority Trial in Healthy Adults on Shortening the Vaccination Schedule From 28 to 7 Days. Clin Infect Dis; Feb 1 2019.Top of Page
							
					
							Last Reviewed:  April 27, 2022						Source: 	National Center for Immunization and Respiratory Diseases
					Facebook
        Twitter
        LinkedIn
        Syndicate homeACIP Home
Meeting Information
Committee Informationplus icon
Role of the ACIP in CDC’s Vaccine Recommendations
Charter
Economics Studies
Committee Membersplus icon
ACIP Membership Roster
Apply for ACIP Membership
Work Groupsplus icon
VaST Reportsplus icon
June 28, 2021
May 24, 2021
May 17, 2021
March 29, 2021
Recommendationsplus icon
Shared Clinical Decision-Making Recommendations
Evidence Based Recommendationsplus icon
About GRADE
Grade Evidence Tables
Evidence to Recommendations Frameworks Vaccines & ImmunizationsImmunization SchedulesVFC ResolutionsVaccine Information Statements (VISs)
  1600 Clifton Road, N.E., Mailstop A27
Atlanta, GA 30329-4027acip@cdc.gov


About CDC
					Contact Us
					800-232-4636
 Facebook Twitter Instagram LinkedIn Youtube Pinterest Snapchat
 CONTACT CDC
				Contact Us
							Call 800-232-4636
							Email Us
			ABOUT CDC
				About CDC
							Jobs
							Funding
			POLICIES
				Accessibility
							External Links
							Privacy
							Policies
							No Fear Act
							FOIA
							OIG
							Nondiscrimination
							Vulnerability Disclosure Policy
			CONNECT WITH US
				Facebook
								Twitter
								Instagram
								LinkedIn
							Youtube
								Pinterest
								Snapchat
								Email
			LANGUAGES
				Español
							繁體中文
							Tiếng Việt
							한국어
							Tagalog
							Русский
							العربية
							Kreyòl Ayisyen
							Français
							Polski
							Português
							Italiano
							Deutsch
							日本語
							فارسی
							English


U.S. Department of Health & Human Services
			Accessibility
			External Links
			Privacy
			Policies
			No Fear Act
			FOIA
			Nondiscrimination
			OIG
			Vulnerability Disclosure Policy
			USA.gov


Exit Notification / Disclaimer Policy Close
 Links with this icon  indicate that you are leaving the CDC website. The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website.
				Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website.
				You will be subject to the destination website's privacy policy when you follow the link.
				CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website. Website Disclaimers
 Cancel Continue