Journal of Global Infectious Diseases

: 2018  |  Volume : 10  |  Issue : 3  |  Page : 159--162

A simple approach to pneumococcal vaccination in adults

Calvin Green, Christine Ann Moore, Akhilesh Mahajan, Kailash Bajaj 
 Department of Internal Medicine, East Tennessee State University James H. Quillen College of Medicine, Johnson City, TN, USA

Correspondence Address:
Dr. Christine Ann Moore
1185 West Mountain View Road, Apartment 1509, Johnson City, TN 37604


Streptococcus pneumoniae is a bacterium responsible for a spectrum of diseases including lobar pneumonia, meningitis, otitis media, and sinusitis. Invasive pneumococcal disease is responsible for significant morbidity and mortality across the world. Concerted efforts led to the development of two vaccinations, Pneumova × 23 and Prevnar 13, for the prevention of pneumococcal disease. The Advisory Committee on Immunization Practices of the US Centers for Disease Control and Prevention provides vaccination schedules for predisposed adults, but the proposed schedules remain a challenge to health-care providers. We performed a systematic review in PubMed and these specialty group websites to present the pathophysiology of pneumococcal disease, outline different pneumococcal vaccinations, and condense recommendations for vaccination administration.

How to cite this article:
Green C, Moore CA, Mahajan A, Bajaj K. A simple approach to pneumococcal vaccination in adults.J Global Infect Dis 2018;10:159-162

How to cite this URL:
Green C, Moore CA, Mahajan A, Bajaj K. A simple approach to pneumococcal vaccination in adults. J Global Infect Dis [serial online] 2018 [cited 2020 Oct 26 ];10:159-162
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Since its identification in the late 19th century by Pasteur and Stenberg, the pneumococcus (Streptococcus pneumoniae) has been associated with an entire spectrum of clinical manifestations, ranging from simple colonization to invasive pneumococcal disease (IPD).[1],[2],[3],[4] In the United States, it is the most common cause of lobar pneumonia; a major cause of meningitis, sinusitis, and otitis media; and a less frequent cause of endocarditis, septic arthritis, and peritonitis.[1],[5],[6],[7] Predisposing factors for IPD are numerous and include the extremes of age, crowding, antecedent viral infections, both anatomic and functional asplenia, chronic disease states such as diabetes mellitus, and frank immunosuppression. Penicillins have been and remain the standard of care; however, drug-resistant S. pneumoniae is now well described in the literature, with acquisition of high-grade resistance thought to originate from spontaneous mutations, horizontal transfer of genetic material across bacterial species, and selective pressure resulting from the indiscriminate use of antibiotics.[8],[9],[10] The emergence of such drug-resistant strains has, for example, led the Infectious Disease Society of America to update their practice guidelines for the management of bacterial meningitis, recommending adjunctive vancomycin when empirically treating presumptive pneumococcal meningitis with a third-generation cephalosporin such as ceftriaxone or cefotaxime.[11]

Given the high burden of IPD, two inactivated, but nonequivalent, vaccines have been developed and marketed for routine vaccination against pneumococcus in adults in the United States: Pneumovax 23 (PPSV23) and Prevnar 13 (PCV13). The Advisory Committee on Immunization Practices (ACIP) of the US Centers for Disease Control and Prevention (CDC) provides guidelines on vaccination scheduling for predisposed adults unvaccinated with either one or both vaccines, but the proposed schedules remain a challenge to health-care providers. The aims of this paper are to clarify the pathophysiology of pneumococcal disease, to provide a balanced overview of different pneumococcal vaccines, and to perform a systematic review to summarize the latest recommendations for pneumococcal vaccination.


S. pneumoniae is a Gram-positive, catalase-negative diplococcus able to be cultured from the human oral mucosa as a commensal but opportunistic organism. The bacterium is fastidious, but routine microbiological identification can be achieved based on in vitro observation of α-hemolysis on blood agar, susceptibility to the chemical optochin, and solubility in bile salts.[1] Most pneumococcal strains are encapsulated, but all have within their cell wall the pneumococcal common antigen (C-polysaccharide), and this antigen can be detected with relative ease in the urine, aiding in the rapid diagnosis of IPD.[12]

Despite conservation of this antigen across pneumococcal strains, sequence variations in capsular antigens have led to the identification of >90 pneumococcal serotypes with distinct differences in their virulence and immunogenicities.[1],[13] Importantly, most are uncommon, and only a small fraction of these cause most cases of invasive disease. Nontypeable (serotype negative) strains are extremely rare in IPD and cause disease in patients with underlying immune defects.[14],[15] Historically, the lower-numbered serotypes have been the most implicated in human disease and both polysaccharide vaccines incorporate capsular material from these prevalent pneumococci.[1] More specifically, PPSV23 and PCV13 share serotypes 1, 3–5, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23, whereas PPSV23 also contains serotypes 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, and 33F.[16],[17] Serotype 6A is unique to PCV13.[1],[16],[17]

 Two Inactivated but Nonequivalent Vaccines

Irrespective of some shared serotypes, PPSV23 and PCV13 also differ in their abilities to generate an effective immune response. Both polysaccharide vaccines generate antibodies against pneumococcal capsular antigens in a T-independent and B-cell-mediated fashion, but only PCV13 can induce a T-cell-dependent response.[13] PCV13, unlike PPSV23, contains a protein conjugate, allowing for a more robust immunogenicity with enhanced avidity and memory for pneumococcal polysaccharide antibodies.[1],[18] Covalent attachment of this nontoxic protein conjugates to the vaccine also allows B-cells to produce antibodies in sufficient amounts to control infection and even reduce or suppress nasopharyngeal colonization with certain vaccine serotypes.[1],[19],[20],[21],[22],[23] Even more, unvaccinated adults have also shown comparable reductions in colonization, suggesting an indirect protection from conjugate vaccines through mechanisms also seen in herd immunization.[1],[3],[18]

Perhaps through immunologic priming, PCV13 also allows for a more enhanced immune response to PPSV23 when administered as the initial vaccine in the vaccination series.[16] Two large, randomized studies demonstrated increased antipneumococcal opsonophagocytosis activities in unvaccinated individuals who were vaccinated with PCV13 but then received PPSV23 12 months later.[1],[19],[24],[25] In contrast, those who first received PPSV23 had a blunted response when later challenged with PCV13, suggesting an immunological advantage seen with the conjugate but not standard polysaccharide vaccine.[1],[18],[24],[25] Based on these observations, the ACIP recommends administering the conjugate vaccine before the standard polysaccharide vaccine in patients who need both.[13],[26]

 Systematic Review of Indications for Vaccination Methods

A systematic review was performed adhering to the guidelines established by the PRISMA statement.[27] A bibliographic search was performed in the PubMed from January 2000 to June 2017 using combinations of the following medical subject heading search terms: “pneumococcal vaccine” or “pneumococcal vaccination.” No prepublished protocol is accessible. Other sources of information were the websites of ACIP and CDC. Four authors (C. G., C. M., A. M., and K. B.) reviewed the articles and achieved consensus. The study was exempt from approval by the Scientific Ethics Committee of Copenhagen Capital Region because the analysis involved only de-identified data. There was no source of funding for this review or preparation of the manuscript.


Although both PCV13 and PPSV23 are FDA approved for use in all adults 50 years and older, the ACIP currently recommends the routine use of the two vaccines in all unvaccinated persons age 65 years or older, with preferential receipt of PCV13 as the initial vaccine followed by administration of PPSV23 6–12 months later.[13],[16],[17],[18],[25] Those who have received PPSV23 before the age of 65 but who are now age 65 or older should receive PCV13 at least 1 year later after the initial dose of PPSV23 and an additional dose of PPSV23 no sooner than 5 years after the initial dose of PPSV23; however, the second dose of PPSV23 should not be administered until at least 12 months after PCV13 vaccination.

The guidelines for patients with certain underlying medical conditions are more complex. Current ACIP recommendations also call for all adults with chronic medical conditions including tobacco use, alcoholism, diabetes mellitus, and chronic heart, lung, or liver diseases, to receive one dose of PPSV23 between 19 and 65 years [Flowchart 1].[18],[26][INLINE:1]

Immunocompromised adults ages 19 or older, including those with functional or anatomic asplenia, should receive both pneumococcal vaccines using a sequential two-dose regimen with PCV13 administered first, followed by a dose of PPSV23 at least 8 weeks later [Flowchart 2]. Other examples of immunocompromised patients at risk for IPD include those with HIV, chronic renal failure or nephrosis, patients with multiple myeloma or generalized malignancies, and those receiving iatrogenic immunosuppression such as solid organ transplant recipients or those receiving prolonged courses of corticosteroids (20 mg of prednisone or its equivalent daily for at least 2 consecutive weeks).[3],[13],[28] Given the increased prevalence of recurrent pneumococcal meningitis in immunocompetent persons with cerebrospinal fluid leaks or cochlear implants, the ACIP also recommends early vaccination in this patient population using the same sequential two-dose regimen as recommended in the immunocompromised.[1],[11],[28],[29][INLINE:2]

 Adverse Reactions and Contraindications

The most common adverse reaction to PPSV23 and PSV13 is noted to be pain or tenderness at site of injection in approximately 60% of patients, progressing to swelling or induration in 20%.[16],[17]

Severe allergic reactions to PPSV23 and PSV13 are contraindication to both the vaccines, whereas a severe allergic reaction to any diphtheria toxoid-containing vaccine is a contraindication for PSV13 only.[16],[17],[30],[31]

 Future Expectations

With the introduction of PCV7 in early 2000, overall IPD incidence declined by 45% (from 24.4 to 13.5 cases per 100,000), and incidence of IPD due to PCV7 strains declined by 94% (from 15.5 to 1.0 cases per 100,000), but incidence of IPD caused by non-PCV7 types (especially S. pneumoniae type 19A) increased marginally, leading to introduction of PCV13 in 2010, which covers a broader range of serotypes.[32],[33]

Now, with the routine use of PCV13 in children aged 2, 4, 6, and 12–15 months of age, there is emergence of non-PCV13 serotypes (for example, 15B, 23A, 23B, and 35B) that appear as colonizers of nasopharynx and as causes of pneumococcal disease, highlighting the need for continued surveillance and updated vaccine.[34],[35] Currently, an additional 15-valent vaccine is undergoing preclinical trial.[36],[37],[38]

The routine use of pneumococcal conjugate vaccine in infants has effectively eradicated nasal colonization of S. pneumoniae vaccine serotypes, not only in vaccinated infants but also in older unvaccinated children and adults due to a phenomenon called “herd immunity.” This has resulted in >90% decline in pneumococcal disease due to serotypes contained in PCV7 among older children and adults who did not receive vaccines.[32] A similar trend has been observed with PCV13 in the United States since 2010 with the same degree of decline in pneumococcal infections in unvaccinated adults. This questions the recommendation for routine use of PCV13 in all adults >65 years of age.[39] Most developed countries (Germany, France, Italy, United Kingdom, etc.) do not recommend the routine use of PCV13 in all adults >65 years of age.[40] The ACIP will reevaluate these in 2018 and revise the guidelines to adjust according to the changing health-care needs of the population.


In this article, we reviewed the basic microbiology and disease spectrum of S. pneumoniae, along with the recent guidelines for vaccination in adults. We hope to improve clinical decision-making and reduce morbidity and mortality in the offices and hospitals. In this study, we observe the evolution of guidelines over the past few years. The trend seen points in the direction that to prevent infections in the general population, to really make a significant difference, the goal is herd immunity, the means to which is achievable through a universally acceptable system of vaccines in the form of vaccination guidelines that are efficient and easily adaptable in day-to-day practice.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1Bennett JE, Dolin R, Blaser MJ. Streptococcus pneumoniae. In: Mandell GL, Douglas JE, Dolin R, editors. Mandell, Douglas, and Bennett's Principles and Practices of Infectious Diseases. 8th ed. Pennsylvania: Elsevier; 2014. p. 2310-27.
2Bogaert D, De Groot R, Hermans PW. Streptococcus pneumoniae colonisation: The key to pneumococcal disease. Lancet Infect Dis 2004;4:144-54.
3Kadioglu A, Weiser JN, Paton JC, Andrew PW. The role of Streptococcus pneumoniae virulence factors in host respiratory colonization and disease. Nat Rev Microbiol 2008;6:288-301.
4Kyaw MH, Rose CE Jr., Fry AM, Singleton JA, Moore Z, Zell ER, et al. The influence of chronic illnesses on the incidence of invasive pneumococcal disease in adults. J Infect Dis 2005;192:377-86.
5Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. Infectious diseases society of America/American thoracic society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007;44 Suppl 2:S27-72.
6Mehr S, Wood N. Streptococcus pneumoniae – A review of carriage, infection, serotype replacement and vaccination. Paediatr Respir Rev 2012;13:258-64.
7Rubins JB, Boulware D, Jano EN. Pneumococcal pneumonia in adults: Epidemiology, clinical features, diagnosis, and therapy. In: Siber G, Klugman KP, Makela P, editors. Pneumococcal Vaccines: The Impact of Conjugate Vaccine. 1st ed. District of Columbia: American Society for Microbiology Press; 2008. p. 117-38.
8Centers for Disease Control and Prevention (CDC). Effects of new penicillin susceptibility breakpoints for Streptococcus pneumoniae – United States, 2006-2007. MMWR Morb Mortal Wkly Rep 2008;57:1353-5.
9Jenkins SG, Farrell DJ. Increase in pneumococcus macrolide resistance, United States. Emerg Infect Dis 2009;15:1260-4.
10Musher DM. Resistance of Streptococcus pneumoniae to Beta-Lactam Antibiotics. UpToDate; 2017.
11Tunkel AR, Hartman BJ, Kaplan SL, Kaufman BA, Roos KL, Scheld WM, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis 2004;39:1267-84.
12Song JY, Eun BW, Nahm MH. Diagnosis of pneumococcal pneumonia: Current pitfalls and the way forward. Infect Chemother 2013;45:351-66.
13Pallotta A, Rehm SJ. Navigating pneumococcal vaccination in adults. Cleve Clin J Med 2016;83:427-33.
14Hanage WP, Kaijalainen T, Saukkoriipi A, Rickcord JL, Spratt BG. A successful, diverse disease-associated lineage of nontypeable pneumococci that has lost the capsular biosynthesis locus. J Clin Microbiol 2006;44:743-9.
15Park IH, Geno KA, Sherwood LK, Nahm MH, Beall B. Population-based analysis of invasive nontypeable pneumococci reveals that most have defective capsule synthesis genes. PLoS One 2014;9:e97825.
16Norcross EW, Sanders ME, Moore QC 3rd, Taylor SD, Tullos NA, Caston RR, et al. Active immunization with pneumolysin versus 23-valent polysaccharide vaccine for Streptococcus pneumoniae keratitis. Invest Ophthalmol Vis Sci 2011;52:9232-43.
17Yeh SH, Gurtman A, Hurley DC, Block SL, Schwartz RH, Patterson S, et al. Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine in infants and toddlers. Pediatrics 2010;126:e493-505.
18Centers for Disease Control and Prevention (CDC). Licensure of 13-valent pneumococcal conjugate vaccine for adults aged 50 years and older. MMWR Morb Mortal Wkly Rep 2012;61:394-5.
19Musher DM. Pneumococcal Vaccination in Adults. UpToDate; 2017.
20Clutterbuck EA, Lazarus R, Yu LM, Bowman J, Bateman EA, Diggle L, et al. Pneumococcal conjugate and plain polysaccharide vaccines have divergent effects on antigen-specific B cells. J Infect Dis 2012;205:1408-16.
21Dagan R, Givon-Lavi N, Zamir O, Sikuler-Cohen M, Guy L, Janco J, et al. Reduction of nasopharyngeal carriage of Streptococcus pneumoniae after administration of a 9-valent pneumococcal conjugate vaccine to toddlers attending day care centers. J Infect Dis 2002;185:927-36.
22Lakshman R, Murdoch C, Race G, Burkinshaw R, Shaw L, Finn A, et al. Pneumococcal nasopharyngeal carriage in children following heptavalent pneumococcal conjugate vaccination in infancy. Arch Dis Child 2003;88:211-4.
23McCool TL, Cate TR, Moy G, Weiser JN. The immune response to pneumococcal proteins during experimental human carriage. J Exp Med 2002;195:359-65.
24Greenberg RN, Gurtman A, Frenck RW, Strout C, Jansen KU, Trammel J, et al. Sequential administration of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine in pneumococcal vaccine-naïve adults 60-64 years of age. Vaccine 2014;32:2364-74.
25Jackson LA, Gurtman A, van Cleeff M, Jansen KU, Jayawardene D, Devlin C, 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 2013;31:3577-84.
26Centers for Disease Control and Prevention. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). Morb Mortal Wkly Rep 2015;64:95-102.
27Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med 2009;6:e1000097.
28Jano EN, Rubins JB. Immunodeficiency and invasive pneumococcal disease. In: Tuomanen EI, Mitchell TJ, Morrison DA, Spratt BG, editors. The Pneumococcus. 1st ed. District of Columbia: American Society for Microbiology Press; 2004. p. 252-80.
29Reefhuis J, Honein MA, Whitney CG, Chamany S, Mann EA, Biernath KR, et al. Risk of bacterial meningitis in children with cochlear implants. N Engl J Med 2003;349:435-45.
30Tomczyk S, Bennett NM, Stoecker C, Gierke R, Moore MR, Whitney CG, et al. Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among patients aged ≥65 years: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morb Mortal Wkly Rep 2014;63:822-5.
31Bonten MJ, Huijts SM, Bolkenbaas M, Webber C, Patterson S, Gault S, et al. Polysaccharide conjugate vaccine against pneumococcal pneumonia in adults. N Engl J Med 2015;372:1114-25.
32Pilishvili T, Lexau C, Farley MM, Hadler J, Harrison LH, Bennett NM, et al. Sustained reductions in invasive pneumococcal disease in the era of conjugate vaccine. J Infect Dis 2010;201:32-41.
33Kaplan SL, Barson WJ, Lin PL, Stovall SH, Bradley JS, Tan TQ, et al. Serotype 19A is the most common serotype causing invasive pneumococcal infections in children. Pediatrics 2010;125:429-36.
34Olarte L, Barson WJ, Barson RM, Lin PL, Romero JR, Tan TQ, et al. Impact of the 13-valent pneumococcal conjugate vaccine on pneumococcal meningitis in US children. Clin Infect Dis 2015;61:767-75.
35Richter SS, Diekema DJ, Heilmann KP, Dohrn CL, Riahi F, Doern GV, et al. Changes in pneumococcal serotypes and antimicrobial resistance after introduction of the 13-valent conjugate vaccine in the United States. Antimicrob Agents Chemother 2014;58:6484-9.
36Rodgers GL, Klugman KP. The future of pneumococcal disease prevention. Vaccine 2011;29 Suppl 3:C43-8.
37Skinner JM, Indrawati L, Cannon J, Blue J, Winters M, Macnair J, et al. Pre-clinical evaluation of a 15-valent pneumococcal conjugate vaccine (PCV15-CRM197) in an infant-rhesus monkey immunogenicity model. Vaccine 2011;29:8870-6.
38McFetridge R, Meulen AS, Folkerth SD, Hoekstra JA, Dallas M, Hoover PA, et al. Safety, tolerability, and immunogenicity of 15-valent pneumococcal conjugate vaccine in healthy adults. Vaccine 2015;33:2793-9.
39Musher DM. Editorial commentary: Should 13-valent protein-conjugate pneumococcal vaccine be used routinely in adults? Clin Infect Dis 2012;55:265-7.
40Ammon A, Catchpole M, Celentano LP. Vaccine scheduler. European Center for Disease Prevention and Control (ECDC). 2017.