Author / Curator: Christopher Steele, MD MPH MS
- 1 Learning Objectives
- 2 Top Teaching Points
- 3 Background
- 4 Management
- 5 Key Trial Summaries
- 6 Ongoing controversies / New updates
- 7 External Resources
- 8 References
(1) Be concise.
(2) Be evidence-based. (Everything should have a reputable citation and resource)(3) Be clinically relevant. (Avoid unnecessary discussion of pathophysiology and epidemiology if it does not help clinical decision-making).
- Define what is a vaccines, and be familiar with the 15 vaccines recommended for adults by the CDC in the United States.
- Understand the eligibility criteria for certain vaccines, including when and how often a dose needs to be administered.
- Learn the common side effects of vaccines, including barriers patients may have from getting them.
- Learn the disease pathogen associated with each vaccine to better educate patients why they are getting the dose.
- Understand the health implications of vaccines.
Top Teaching Points
- Vaccines are estimated to prevent 2-3 million deaths annually.
- Vaccines led to the eradication of small pox in 1980, with the last case documented in Somalia in 1977.
- Vaccines do not cause autism. The report of flu-like symptoms after an immunization is evidence the body is developing immunity to that agent. 
- Herd immunity occurs when ~90-95% of the population is vaccinated for a particular agent. This phenomenon protects those who cannot be immunized since so many people are immune it is difficult for the pathogen to spread effectively to be infectious.
- The flu shot is recommended for all patients who are 6 months or older annually unless they had a history of Guillian-Barré syndrome, anaphylaxis to the vaccine or egg products. This includes giving the vaccine to people with self-limiting illness.
- The three live attenuated vaccines offered to the general population are MMR, Zoster and Varicella.
- The three populations that should not receive live attenuated vaccine are 1) Pregnant women; 2) Immunocompromised excluding HIV patients 3) and AIDS patients (CD4 count < 200 cells/μL.)
- Tetanus, diphtheria and acellular pertussis (TDaP) vaccine should be boosted very 10 years with just tetanus and diphtheria (TD) except in pregnant women who should receive TDaP to protect their future child.
- Gardasil (quadrivalent HPV vaccine) results in a ~90% reduction in incidence of genital warts, 45% reduction in low grade cervical dysplasia and 85% reduction in high-grade cervical dysplasia of the agents causing cervical cancer. 
- Primary care physicians are recommended to refer their patients to an infectious disease travel clinic for patients traveling outside the country.
The following sections discuss the guidelines on vaccinations for adult patients ≥ 18 years or older.
The World Health Organization (WHO) defines a vaccine as a biological agent that aides in the development of immunity to certain pathogens. Vaccines can be thought of as an agent that helps the body generate protection against a certain illness without actually being infected with that pathogen. It is estimated that vaccines prevent nearly 2 to 3 million deaths annually. Another major benefit from vaccines is the herd immunity effect, which occurs when ~90-95% of the population is vaccinated for a particular agent. This phenomenon is important to protect the population who cannot be immunized such as young children or immunocompromised.
Currently, there are 15 communicable diseases that the CDC recommends vaccination for adults depending on their risk factors. They are influenza, tetanus, diphtheria (TD), acellular pertussis (TDaP), varicella, human papilloma virus (HPV), zoster, measles, mumps, rubella (MMR), pneumococcal (23 and 13 valiant form), meningococcal, haemophilus influenza, hepatitis A and hepatitis B. There are other vaccines such as yellow fever and rabies that are offered to certain populations that will not be discussed in this review.
It is the responsibility of health care providers to ensure patients are both up to date, but also address barriers to obtaining vaccines. For practitioners, the most important teaching point is knowing which illnesses confer a high-risk state. Table 1 summarizes high risk patients who deserve special consideration for vaccines
|Table 1: High Risk Patients Who Deserve Special Consideration for Vaccines|
|Age||Age ≥ 65 or older|
|Health Conditions||Asplenia, ESRD, certain chronic lung, liver and heart disease (e.g. COPD, cirrhosis, Hepatitis B or C or heart failure)|
|Risky Social Behaviors||Alcoholism, smokers, sex workers, IV drug users|
|Immunocompromised||HIV/AIDs patients, transplant patients, those on chronic immunosuppressive therapy (e.g. cancer or rheumatology therapy such as Eculizumab).|
|Other||Pregnant women, men who have sex with men|
The most common side effect from a vaccine is local site tenderness and swelling at the site of injection. Some patients may develop side effects such as a low-grade fever, aches or chills which is actually your body developing immunity to the agent. Patients with self-limiting illnesses should still obtain vaccines. In general, inactivated vaccines, or vaccines with agents that are not alive, pose no risk to at risk populations. The three live attenuated vaccines offered to the general population are MMR, Zoster and Varicella. Those who should not receive live attenuated vaccines are 1) Pregnant women; 2) Immunocompromised excluding HIV patients 3) AIDs patients (CD4 count < 200 cells/μL.) Some patients and parents may choose not to vaccinate their children secondary to fear of side effects. The most famous paper was by Dr. Wakefield in 1998 claiming that there was an increased incidence of autism and colitis with MMR resulting in numerous parents choosing to not immunize their children.  This paper was later retracted and numerous studies have proven that vaccines do not cause autism. Once considered eliminated in the USA as early as 2000, the Wakefield paper is responsible for the reintroduction of measles with 118 reported cases in 2017 and as high as 667 cases in 2014. The last reported death from measles in the USA was 2015.
Another reason why patients choose not to get vaccinated is the lack of understanding what they are obtaining protection from and the risks associated with that particular agent if they were to get infected. It is important that practitioners take the time to explain what these illnesses are, and the risk a patient may acquire if they were to be infected by that pathogen.
Finally, patients traveling to high risk areas outside the United States should visit a travel medicine clinic to obtain additional vaccines that may protect them from pathogens endemic to that area that may not be present in the United States.
The following sections will be an overview of the vaccines offered to adults, including special considerations for each population.
The following is a summary of the vaccine schedule for adults as recommended by the CDC:https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html#f6
- The influenza vaccine protects against the influenza virus which typically causes a high-fever viral illness.
- On average, the vaccine is effective for 2 out of every 3 patients in a given year.
- Flu vaccine itself usually protects against 3 to 4 strains which is a mix of influenza A and B.
- Eligibility and Scheduling: The flu shot is recommended for all patients once who are 6 months or older annually usually around mid-fall to late winter. Vaccine is contraindicated with patients who have a history of Guillian-Barré syndrome, anaphylaxis to the vaccine or egg products.
- Mild illnesses should not preclude someone from getting the flu shot.
- The most common side effect is local site tenderness and swelling at the injection site. The flu shot does not cause the flu but the body may develop mild flu-like symptoms when acquiring immunity to the vaccine.
- The pneumococcal vaccines protects against Streptococcus pneumonia. Streptococcus pneumonia is a common nosocomial pathogen that can result in serious infectious such as sepsis, pneumonia, and meningitis.
- There are two pneumococcal vaccines pneumococcal polysaccharide vaccine (PPSV) 23 and pneumococcal conjugate vaccine (PCV) 13.
- Patients eligible for PPSV 23: All adults ≥ 65 or older, or adults ages <65 with a high-risk state as discussed in the background section above.
- Patients eligible for PCV 13: Adults who are a high-risk state except with certain chronic conditions as defined above, history of a CSF leaks or cochlear implants.
- Adults ≥ 65 or older: Immunocompetent patients should get PCV13 and PPSV23 one year from another. Patients who are immunocompromised should get PCV13 first, then PPSV23 8 weeks after
- Patients with diabetes, chronic heart, liver or lung conditions, ESRD, alcoholism or smoking (age <65): Give PPSV23 first, wait one year and then give PCV13. Repeat PPSV23 at age 65 or older with at least 5 years from the previous vaccination administration.
- Patients with asplenia, sickle cell, HIV/AIDS, CSF leak or cochlear implants (age <65): PCV13 then 8 weeks later PPSV23. Repeat PPSV23 at age 65 or older with at least 5 years from the previous vaccination administration.
- PPSV should be given a year after PCV13 was given and PCV 13 should be given 8 weeks after PPSV23.
- HPV is responsible for genital warts and cancer of the cervix, vulva, penis, anus and throat.
- There are 3 vaccines, a bivalent, quadrivalent and 9-valiant vaccine. Gardasil is the most common and protects against strains 6, 11, 16, 18. The first two are more pathogenic for warts while 16, and 18 protect against cancer.
- Eligibility: Vaccination schedule varies by sex. Females are recommended to be vaccinated through age 26 years while males through age 21 years. Male patients ages 22 and 26 should be offered the HPV vaccine but it is not required to obtain it.
- Scheduling: 3 dose series, given usually at 0, 2 and 6 month intervals.
- Gardasil results in a ~90% reduction in incidence of genital warts, 45% reduction in low grade cervical dysplasia and 85% reduction in high-grade cervical dysplasia of the agents causing cervical cancer. 
- More research should be done to determine if HPV vaccines benefit those over the age of 26.
- Tetanus, diphtheria and acellular pertussis (TDaP) and the tetanus diphtheria (TD) vaccines are offered.
- Eligibility: All adults who never received TDaP should get one dose.
- Scheduling: All adults who have had TDaP should get a TD booster every 10 years.
- Pregnant women are recommended to get TDaP vaccination while pregnant during weeks 27-36 to provide immunity to their child to pertussis. TDaP is not recommended currently by the CDC for the partner. 
Measles Mumps and Rubella
- Eligibility: Administer 1 dose to adults who demonstrate they do not have immunity and health care workers who demonstrate no immunity to MMR.
- This would include patients who may have had the shot and lost immunity over the years as evidence in blood work.
- Give MMR vaccine to post-partum women as they are leaving the hospital.
- Contraindications: MMR is contraindicated in 1) Pregnant women; 2) Immunocompromised excluding HIV patients 3) and AIDS patients (CD4 count < 200 cells/μL.)
- Zoster Vaccine protects against shingles, a condition also known as herpes zoster where patients develop a painful rash along a dermatome of the skin, usually unilaterally.
- Two forms, recombinant zoster vaccine (RZV) and Zoster Vaccine Live (ZVL). RZV is the recommended vaccine and should be the one administered.
- Eligibility: All adults 50 or older should get 2 doses of RZV 2-6 months apart from one another.
- Contraindications: ZVL is contraindicated in 1) Pregnant women; 2) Immunocompromised excluding HIV patients 3) and AIDS patients (CD4 count < 200 cells/μL.)
- Varicella vaccine (VAR) protects against varicella or chicken pox.
- Eligibility: All adults who demonstrate no immunity to varicella.
- Most adults born before 1980 have immunity from exposure
- Contraindications: VAR is contraindicated in 1) Pregnant women; 2) Immunocompromised excluding HIV patients 3) and AIDS patients (CD4 count < 200 cells/μL.)
- Hepatitis A: Vaccinate only high-risk patients such as men who have sex with men, chronic liver disease, hepatitis B or C infection, clotting factor disorder, and those traveling to an endemic area.  
- Havrix: 2 doses 0 and 6-12 months apart
- Twinrix: (includes hepatitis B): 0, 1 and 6 months apart.
- Hepatitis B: Vaccinate only high-risk patients such as men who have sex with men, high risk sexual behaviors, exposure to someone with HBV through blood, HIV infection, cirrhosis, hepatitis B or C infection, clotting factor disorder, and those traveling to an endemic area. 
- Twinrix (includes hepatitis A): 0, 1 and 6 months apart.
- HepB single antigen (HepB): o, 1 and 6 months apart.
- Meningococcal vaccination: 2 dose quadrivalent vaccine given 8 weeks apart that should be given to first-year college students, military recruits, immunocompromised states, patients receiving eculizumab, and those either traveling to or exposed to an area with meningococcal disease. 
- Haemophilus influenza(Hib): Currently only recommended in two conditions:
- 1 dose for asplenic patients
- 3 doses a month apart from one another for hematopoietic stem cell transplant patients.
Key Trial Summaries
- Ebola Ça Suffit! (2016)- This study looked at the effectiveness of rVSV-ZEBOV, or the Ebola vaccine. In short, the group found initial clusters of people who were exposed to the ebola virus and offered them either an immediate vaccine or a 21-day delayed vaccine. In short, it was 100% effective with 2119 participants in the immediate vaccine group, 2041 participants in the delayed vaccine group with 16 cases occurring among those who were in the delayed cluster who chose not to be vaccinated. The trial again took those in contact with those 16 people and vaccinated all the willing participants (1667) with again 100% immunity.
- HIV1 Vaccine (2005)- A double-blind randomized clinical trial was run with a total of 5403 volunteers (5095 men and 308 women) to study immunity to HIV 1 vaccine. In summary, the vaccine did not prevent HIV-1 acquisition: infection rates were 6.7% in 3598 of those vaccinated and 7.0% in 1805 placebo recipients.
- PCV13 VS PPSV23 (2013)- A randomized, modified double-blind trial compared a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) with 23-valent pneumococcal polysaccharide vaccine (PPSV23) in 831 pneumococcal vaccine naive adults 60-64 years of age. An additional group of 403 adults 50-59 years of age received open-label PCV13. Anti-pneumococcal opsonophagocytic activity (OPA) titers were measured at baseline, and at 1 month and 1 year after vaccination. It was found that OPA mean titers in the PCV13 group were statistically significantly higher than in the PPSV23 group for 8 of the 12 serotypes common to both vaccines. It concluded that PCV13 induces a greater functional immune response than PPSV23 for the majority of serotypes covered by PCV13, suggesting that PCV13 could offer immunological advantages over PPSV23 for prevention of vaccine-type pneumococcal infection.
- HPV Quadrivalent vaccine (2007)- In a randomized, double-blind trial, 12,167 women between the ages of 15 and 26 years received 3 doses of either a quadrivalent vaccine that included HPV 6, 11, 16 and 18 or placebo administered at 0, 2 and 6 months apart. Over 3 years from the first dose, those in the vaccinated group were 98% (95.89% confidence interval [CI], 86 to 100) did not develop cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, or cervical cancer while only 44% in the placebo group. They concluded that this vaccine was successful at reducing pre-cancerous and cancerous complications from HPV. 
Ongoing controversies / New updates
- The live attenuated intranasal flu vaccine will be reissued in the 2018-209 flu season.
- Taylor LE et al. Vaccines Are Not Associated with Autism: An Evidence-based Meta-analysis of Case-control and Cohort Studies. Vaccine 2014;32(29):3623–9.
- Wakefield A, Murch S, Anthony A; et al. (1998). "Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children". The Lancet. 351 (9103): 637–41.
- Uno Y et al. Early Exposure to the Combined Measles-Mumps-Rubella Vaccine and Thimerosal-containing Vaccines and Risk of Autism Spectrum Disorder. Vaccine 2015;33(21):2511-6.
- Jain A et al. Autism Occurrence by MMR Vaccine Status among US Children with Older Siblings with and without Autism. JAMA 2015;313(15):1534-40.
- Demicheli V et al. Vaccines for Measles, Mumps and Rubella in Children. Cochrane Database Syst Rev. 2012 Feb 15.
- Immunization Safety Review: Adverse Effects of Vaccines: Evidence and Causality. Institute of Medicine. The National Academies Press: 2011. Consensus Report.
- Mrozek-Budzyn D et al. Lack of Association Between Measles-Mumps-Rubella Vaccination and Autism in Children: A Case-Control Study. Pediatr Infect Dis J. 2010;29(5):397-400.
- Baird G et al.Measles Vaccination and Antibody Response in Autism Spectrum Disorders. Arch Dis Child 2008; 93(10):832-7. S
- Hornig M et al. Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study. PLoS ONE 2008; 3(9):e3140.
- Doja A, Roberts W. Immunizations and Autism: A Review of the Literature. Can J Neurol Sci. 2006; 33(4):341-6.
- D’Souza Y et al. No Evidence of Persisting Measles Virus in Peripheral Blood Mononuclear Cells from Children with Autism Spectrum Disorder. Pediatrics 2006; 118(4):1664-75.
- Uchiyama T et al. MMR-Vaccine and Regression in Autism Spectrum Disorders: Negative Results Presented from Japan.J Autism Dev Disord 2007; 37(2):210-7.
- Fombonne E et al. Pervasive Developmental Disorders in Montreal, Quebec, Canada: Prevalence and Links with Immunizations. Pediatrics. 2006;118(1):e139-50.
- Richler J et al. Is There a ‘Regressive Phenotype’ of Autism Spectrum Disorder Associated with the Measles-Mumps-Rubella Vaccine? A CPEA Study. J Autism Dev Disord. 2006 Apr;36(3):299-316.
- Klein KC, Diehl EB. Relationship between MMR Vaccine and Autism. Ann Pharmacother. 2004; 38(7-8):1297-300
- Immunization Safety Review: Vaccines and Autism. Institute of Medicine. The National Academies Press: 2004.
- Smeeth L et al. MMR Vaccination and Pervasive Developmental Disorders: A Case-Control Study. Lancet 2004; 364(9438): 963-9.
- DeStefano F et al. Age at First Measles-Mumps-Rubella Vaccination in Children with Autism and School-Matched Control Subjects: A Population-Based Study in Metropolitan Atlanta. Pediatrics 2004; 113(2): 259-66.
- Lingam R et al. Prevalence of Autism and Parentally Reported Triggers in a North East London Population. Arch Dis Child 2003; 88(8):666-70.
- Madsen KM et al. A Population-Based Study of Measles, Mumps, and Rubella Vaccination and Autism. N Engl J Med 2002; 347(19):1477-82.
- Makela A et al. Neurologic Disorders after Measles-Mumps-Rubella Vaccination. Pediatrics 2002; 110:957-63.
- Black C et al. Relation of Childhood Gastrointestinal Disorders to Autism: Nested Case Control Study Using Data from the UK General Practice Research Database. BMJ 2002; 325:419-21.
- Taylor B et al. Measles, Mumps, and Rubella Vaccination and Bowel Problems or Developmental Regression in Children with Autism: Population Study. BMJ 2002; 324(7334):393-6.
- Fombonne E et al. No Evidence for a New Variant of Measles-Mumps-RubellaInduced Autism. Pediatrics 2001;108(4):E58.
- Dales L et al. Time Trends in Autism and in MMR Immunization Coverage in California. JAMA 2001; 285(9):1183-5.
- Kaye JA et al. Mumps, Measles, and Rubella Vaccine and the Incidence of Autism Recorded by General Practitioners: A Time Trend Analysis. BMJ 2001; 322:460-63.
- Taylor B et al. Autism and Measles, Mumps, and Rubella Vaccine: No Epidemiological Evidence for a Causal Association. Lancet 1999;353 (9169):2026-9.
- Prevention and Control of Seasonal Influenza with Vaccines Recommendations of the Advisory Committee on Immunization Practices — United States, 2016–17 Influenza Season. MMWR; August 26, 2016;65(5);1-54
- Osterholm, Michael T; Kelley, Nicholas S; Sommer, Alfred; Belongia, Edward A (2012). "Efficacy and effectiveness of influenza vaccines: A systematic review and meta-analysis". The Lancet Infectious Diseases. 12 (1): 36–44.
- "ACIP votes down use of LAIV for 2016-2017 flu season"
- Kobayashi M, Bennett NM, Gierke R, Almendares O, Moore MR, Whitney CG, et al. Intervals between PCV13 and PPSV23 vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2015;64(34):944-7.
- Tomczyk S, Bennett NM, Stoecker C, Gierke R, Moore MR, Whitney CG, et al. Use of PCV-13 and PPSV-23 vaccine among adults aged 65 and older: recommendations of the ACIP. MMWR. 2014;63(37);822-5.
- Use of PCV13 and PPSV23 Vaccine for Adults with Immunocompromising Conditions. MMWR, October 12, 2012, Vol 61, #40.
- Jackson LA et al. Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine compared to a 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine-naive adults. Vaccine. Volume 31, Issue 35, August 2013, Pages 3577-3584.
- Quadrivalent Human Papillomavirus Vaccine: Recommendations of ACIP. MMWR, March 23, 2007, Vo1 56, #RR02
- FDA Licensure of Bivalent Human Papillomavirus Vaccine (HPV2, Cervarix) for Use in Females and Updated HPV Vaccination Recommendations from ACIP. MMWR, May 28, 2010, Vo1 59, #20
- Quadrivalent Human Papillomavirus Vaccine (HPV4, Gardasil) for Use in Males and Guidance from ACIP. MMWR, May 28, 2010, Vo1 59, #20
- Updated Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis (Tdap) Vaccine in Adults Aged 65 Years and Older, ACIP 2012. MMWR, June 29, 2012, Vol 61, #25
- Preventing Tetanus, Diphtheria, and Pertussis Among ADULTS: Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccines. MMWR, December 15, 2006, Vol 55, #RR-17
- Updated Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccine (Tdap) in Pregnant Women – ACIP, 2012. MMWR, February 22, 2013, Vol 62, #7
- Prevention of Hepatitis A Through Active or Passive Immunization. MMWR, May 19, 2006, Vol 55, #RR-07
- Update: Prevention of Hepatitis A After Exposure to Hepatitis A Virus and in International Travelers. Updated Recommendations of the ACIP. MMWR, October 19, 2007, Vol 56, #41
- Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR, January 12, 2018, Vol 67,(1);1-31
- Updated Recommendations for Use of Meningococcal Conjugate Vaccines — ACIP, 2010. MMWR, January 28, 2011, Vol 60, #03
- Henao-Restrepo A et. al. Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Lancet Volume 389, No. 10068, p505–518, 4 February 2017.
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- The FUTURE II Study Group. Quadrivalent Vaccine against Human Papillomavirus to Prevent High-Grade Cervical Lesions. N Engl J Med 2007; 356:1915-1927.