Pneumococcal conjugate vaccine for HIV-infected adults

Issue: BCMJ, vol. 57, No. 2, March 2015, Page 62 BC Centre for Disease Control
By: Monika Naus, MD, MHSc, FRCPC, FACPM

British Columbia is expanding use of pneumococcal conjugate 13-valent vaccine (PCV13, Prev-nar 13) to HIV-infected adults starting in April 2015. Since June 2010, the vaccine has been in use for routine immunization of infants and healthy children under age 5, replacing the pneumococcal conjugate 7-valent vaccine (PCV7). In 2013 the National Advisory Committee on Im-munization (NACI) issued an updated statement on use of pneumococcal conjugate vaccine in high-risk adults.[1] In addition to haematopoietic stem cell transplant recipients (HSCT, covered in the BC program), the only other individuals for whom the committee assessed the evidence as “good” are those with HIV infection. One dose of PCV13 followed by one dose of pneumococcal polysaccharide 23-valent vaccine (PPV23) at least 8 weeks later is recommended. For those who have received PPV23 in the prior year, NACI recommends waiting 1 year to give the dose of PCV13. A total of two lifetime doses of PPV23 is recommended, with the second dose given 5 years after the first dose of PPV23. PPV23 continues to be recommended in HIV-infected adults because about 38% of reported cases of invasive pneumococcal disease among adults in British Columbia are due to serotypes covered only by PPV23; 25% are due to serotypes not contained in either PCV13 or PPV23 (source: BCCDC data on file).

Detailed recommendations for the use of these vaccines are contained in the BC immunization manual available at www.bccdc.ca/dis-cond/comm-manual/CDManualChap2.htm.

There has been longstanding interest in improved protection against pneumococcal disease, which remains an important infection across the age span. Reported rates of invasive pneumococcal disease in BC are about 8 per 100 000, but in infants and adults 60 and older the rates in 2013 were 18.5 and 20 per 100 000, respectively.[2] The US Centers for Disease Control estimates that the rate among HSCT recipients is 186 and among HIV-positive people is 173 per 100 000.[3] A record linkage study in southern Alberta identified a rate of invasive pneumococcal disease of 342 per 100 000 person-years among HIV-positive individuals, which was reduced to 187 per 100 000 within 3 years of PPV23 immunization. Although 75% of cases had received PPV23, 74% of invasive pneumococcal disease episodes were due to PPV23 serotypes.[4] While the polysaccharide 23-valent vaccines provide a better spectrum of serotype coverage, these produce a T-cell independent immune response, which does not result in immunologic memory; as well, the resultant antibodies have lower avidity than those generated by protein-polysaccharide conjugate vaccines.[5] Conjugate vaccines were developed to produce effective protection in young children and have been associated with reduction in nasopharyngeal carriage and herd immunity. Conjugate vaccines are also not associated with hyporesponsiveness or blunting of the immune response with subsequent doses, which has been observed in studies of polysaccharide vaccines (meningococcal, Hib, and pneumococcal) including one study among HIV-infected adults in Uganda, which was terminated early because of concern about higher rates of invasive pneumococcal disease among prior PPV23 recipients.[6] While this phenomenon is not well understood and may vary by pneumococcal serotypes and the unique immunogenetic profile of the host, these concerns are overcome by priming with conjugate vaccines.

There are no efficacy or effectiveness studies of PCV13 in HIV-infected adults, and recommendations are based on a study of PCV7 efficacy in HIV-infected adolescents and adults in Malawi with a prior episode of invasive pneumococcal disease in whom clinical protection against invasive pneumococcal disease of 75% (95% CI, 29%-92%) was observed,[7] and several studies in Europe and the US of immunogenicity and safety of PCV7. In one such study, the prime-boost strategy of PCV7 followed by PPV23 was seen to result in a higher proportion of recipients achieving a twofold or greater rise in serotype specific IgG and antibody levels greater than or equal to 1 µg/mL compared to PPV23 vaccine alone; this phenomenon was also seen in smokers and those with hepatitis C infection, in whom the immune response was blunted in both groups but higher in the prime-boost group compared with those receiving only polysaccharide vaccine.[8] The duration of protection of this series is still unknown.
—Monika Naus, MD, MHSc

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This article is the opinion of the BC Centre for Disease Control and has not been peer reviewed by the BCMJ Editorial Board.

References

1.    National Advisory Committee on Immunization. Statement on the use of conjugate pneumococcal vaccine – 13 valent in adults (PNEU-C-13). CCDR 2013;39(ACS-5):1-52.
2.    BC Centre for Disease Control. 2013 Annual summary of reportable diseases. Pneumococcal disease, invasive: pages 25-27. Accessed 2 February 2015. www.bccdc.ca/util/about/annreport/default.htm. 
3.    Bennett NM, Advisory Committee on Immunization Practices Pneumococcal Work Group, Whitney CG, et al. 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). MMWR 2012;61:816-819.
4.    Siemieniuk RAC, Gregson DB, Gill MJ. The persisting burden of invasive pneumococcal disease in HIV patients: An observational cohort study. BMC Infect Dis. 2011;11:314.
5.    Pichichero ME. Protein carriers of conjugate vaccines: characteristics, development, and clinical trials. Hum Vaccin Immunother. 2013;9:2505-2523.
6.    O’Brien KL, Hochman M, Goldblatt D. Combined schedules of pneumococcal conjugate and polysaccharide vaccines: Is hyporesponsiveness an issue? Lancet Infect Dis 2007;7:597-606.
7.    French N, Gordon SB, Mwalukomo T, et al. A trial of a 7-valent pneumococcal conjugate vaccine in HIV-infected adults. N Engl J Med 2010;362:812-822.
8.    Lesprit P, Pedrono G, Molina JM, et al. Immunological efficacy of a prime-boost pneumococcal vaccination in HIV-infected adults. AIDS 2007;21:2425-2434.

Monika Naus, MD, MHSc, FRCPC, FACPM. Pneumococcal conjugate vaccine for HIV-infected adults. BCMJ, Vol. 57, No. 2, March, 2015, Page(s) 62 - BC Centre for Disease Control.


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