6.2 ACIP Adult Non-Respiratory Vaccines: Tdap, Shingrix, HPV & Hep B

Tetanus, Diphtheria, and Pertussis (Tdap / Td)

Microbiology and Clinical Manifestations

• Clostridium tetani: An obligate anaerobic, spore-forming, gram-positive bacillus found ubiquitously in soil, animal feces, and road dust. Spores enter broken skin and germinate under anaerobic conditions. Vegetative cells release tetanospasmin, an extremely potent neurotoxin that undergoes retrograde intraneuronal transport to the spinal cord and brainstem. Tetanospasmin cleaves synaptobrevin, blocking the release of inhibitory neurotransmitters (gamma-aminobutyric acid [GABA] and glycine) from Renshaw interneurons. This leads to unregulated, continuous alpha-motor neuron firing manifesting as painful trismus ("lockjaw"), risus sardonicus, generalized muscle spasms, painful opisthotonos, autonomic lability, and respiratory arrest.
• Corynebacterium diphtheriae: An aerobic gram-positive bacillus that produces diphtheria toxin (an ADP-ribosylating toxin inactivating elongation factor EF-2). Clinical manifestations include a dense, gray, adherent fibrinous pseudomembrane over the tonsils and pharynx, myocarditis with conduction block, and cranial/peripheral neuropathies.
• Bordetella pertussis: A fastidious gram-negative coccobacillus producing pertussis toxin, filamentous hemagglutinin, and tracheal cytotoxin. Causes whooping cough, characterized by a catarrhal phase progressing to a paroxysmal phase of intense coughing spasms with post-tussive emesis, subconjunctival hemorrhages, rib fractures, and syncope.

Routine Adult Schedule

• Primary Adult Booster: All adults aged 19 and older who have not previously received a dose of Tdap (tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis) should receive 1 lifetime dose of Tdap.
• Decennial Maintenance: Following the initial Tdap dose, adults should receive a booster dose of either Td or Tdap every 10 years. (ACIP guidelines explicitly state that Tdap may be used interchangeably with Td for decennial boosters, wound management, and catch-up regimens).

Maternal Pertussis Immunization

• Mandate: Pregnant individuals must receive a dose of Tdap during EACH and EVERY pregnancy, regardless of the patient's prior vaccination history or the interval since their previous Td or Tdap booster.
• Optimal Timing: Administered between 27 and 36 weeks of gestation (optimally early in this window, between 27 and 32 weeks).
• Mechanism: Tdap stimulates peak maternal anti-pertussis IgG antibodies, which actively cross the placenta via the neonatal Fc receptor (FcRn). This confers high levels of protective transplacental antibodies to the newborn, shielding the infant against severe pertussis, apnea, encephalopathy, and death during the critical first 2 months of life before the infant can receive their first DTaP dose at 2 months.
• Postpartum Catch-Up: If Tdap was not administered during pregnancy, it should be administered immediately postpartum prior to discharge ("cocooning" strategy), although passive placental transfer during pregnancy provides significantly superior infant protection.

Tetanus Wound Management Algorithm

Evaluating acute traumatic lacerations requires assessing both the wound characteristics (clean/minor vs contaminated/dirty) and the patient's tetanus vaccination history:

• Contaminated / Dirty Wounds: Wounds contaminated with soil, feces, dirt, or saliva; puncture wounds (e.g., rusted nails, animal bites); avulsions; wounds resulting from crushing, burns, or frostbite; and wounds with devitalized tissue.
• Clean and Minor Wounds: Superficial, non-penetrating abrasions or clean incisions without particulate contamination or tissue devitalization.

[!IMPORTANT] Administration Rule for TIG: When both tetanus vaccine (Td or Tdap) and Tetanus Immune Globulin (TIG, 250 units IM) are indicated, they must be administered at separate anatomical sites (e.g., opposite deltoids or deltoid and gluteus) using separate syringes to avoid direct antigen-antibody neutralization.

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Recombinant Zoster Vaccine (RZV, Shingrix)

Pathophysiology of Herpes Zoster & Complications

Primary infection with Varicella Zoster Virus (VZV) causes chickenpox, after which the virus establishes lifelong latency within sensory cranial nerve and dorsal root ganglia. With advancing age or immunosuppression, VZV-specific cell-mediated CD4+ T-cell immunity declines, allowing viral replication, ganglionitis, and anterograde migration down sensory axons to the skin. This manifests as a painful, unilateral, dermatomal maculopapular eruption that rapidly evolves into grouped vesicles.

• Postherpetic Neuralgia (PHN): The most frequent chronic complication, defined as persistent dermatomal neuropathic pain lasting >90 days after the onset of the rash. PHN occurs in up to 20–30% of zoster patients over age 60 and can persist for months to years, causing severe debilitation.
• Herpes Zoster Ophthalmicus (HZO): Reactivation involving the ophthalmic division (V1) of the trigeminal nerve. The presence of vesicles on the tip or side of the nose (Hutchinson's sign) indicates involvement of the nasociliary branch and strongly correlates with ocular complications (keratitis, anterior uveitis, secondary glaucoma, permanent visual loss), requiring immediate ophthalmology consultation.

Vaccine Biology & Efficacy

• Formulation: Recombinant Zoster Vaccine (RZV, Shingrix) is an adjuvanted, non-live sub-unit vaccine containing 50 μg of recombinant VZV glycoprotein E (gE) lyophilized antigen reconstituted with the AS01B adjuvant system.
• Adjuvant AS01B: Formulated with QS-21 (a triterpene glucoside saponin) and 3-O-desacyl-4'-monophosphoryl lipid A (MPL, a TLR4 agonist) in a liposomal suspension. This adjuvant strongly activates dendritic cells and induces exceptionally high, durable frequencies of gE-specific CD4+ T cells.
• Clinical Efficacy: Shingrix demonstrates >90–97% efficacy in preventing herpes zoster and PHN across all adult age brackets (including patients ≥ 80 years), maintaining >85% efficacy at 10 years post-vaccination.
• Retirement of Zostavax: The live attenuated zoster vaccine (Zostavax, ZVL) was permanently discontinued in the United States in November 2020 due to low initial efficacy (<51% overall, <38% in age ≥ 70), rapid waning, and strict contraindications in immunocompromised hosts.

Target Populations and Dosing Regimens

• Immunocompetent Adults Aged ≥ 50 Years: 2 doses of Shingrix administered intramuscularly (0.5 mL each) separated by 2 to 6 months.
• Immunocompromised Adults Aged ≥ 19 Years: 2 doses of Shingrix administered intramuscularly separated by 1 to 2 months (the accelerated interval ensures completion prior to planned immunosuppression or chemotherapy).
• Prior Herpes Zoster Episode: Patients with a documented history of shingles should still be vaccinated. Recurrence rates after natural zoster are significant. Vaccination should be administered once the acute zoster rash has fully resolved and crusted.
• Prior Zostavax Recipients: Adults who previously received Zostavax should be revaccinated with the complete 2-dose Shingrix series, waiting at least 2 months after the Zostavax dose.
• Varicella Serologic Screening: Pre-vaccination serologic testing for varicella immunity is not recommended for adults aged ≥ 50; >99% of individuals born in the US before 1980 have had wild-type varicella.

Reactogenicity and Patient Counseling

Shingrix induces substantial local and systemic reactogenicity due to the potent AS01B adjuvant:

• Local Reactions: Injection site pain occurs in up to 78% of recipients, with redness and swelling in 30–40%.
• Systemic Reactions: Fatigue, myalgias, headache, and low-grade fever occur in 10–15% of patients, typically lasting 1 to 3 days.
• Clinical Pearl: Proactive pre-vaccination counseling is vital. Explain to patients that acute local soreness and flu-like symptoms are expected physiological indicators of strong immune activation, are self-limiting, and do not represent active herpes zoster or a contraindication to receiving the mandatory second dose.

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Human Papillomavirus (9vHPV, Gardasil 9)

Virology, Oncogenesis, and Serotype Stratification

Human papillomavirus is a small, non-enveloped, double-stranded circular DNA virus infecting mucosal and cutaneous basal keratinocytes. Persistent infection with high-risk oncogenic types drives malignant transformation through viral oncoproteins E6 (which targets the p53 tumor suppressor protein for proteasomal degradation) and E7 (which binds and inactivates the retinoblastoma tumor suppressor protein Rb, releasing E2F transcription factors to drive unregulated cell division).

• High-Risk Oncogenic Types: Types 16 and 18 cause approximately 70% of invasive cervical cancers and a high proportion of anal, oropharyngeal, vulvar, vaginal, and penile cancers. Types 31, 33, 45, 52, and 58 account for an additional 20% of cervical cancers.
• Low-Risk Non-Oncogenic Types: Types 6 and 11 cause >90% of anogenital warts (condylomata acuminata) and recurrent respiratory papillomatosis.

9-Valent HPV Vaccine (Gardasil 9)

Formulated with recombinant virus-like particles (VLPs) of the L1 major capsid protein of types 6, 11, 16, 18, 31, 33, 45, 52, and 58, adsorbed onto an aluminum adjuvant. It provides comprehensive prophylaxis against approximately 90% of cervical cancers and 90% of genital warts.

Age-Based Recommendations and Shared Clinical Decision-Making

• Routine Vaccination (Through Age 26 Years): Universally recommended for all individuals (males and females) through age 26. Routine vaccination is routinely initiated at age 11–12 years (can start as early as age 9).
• Adults Aged 27 Through 45 Years (Shared Clinical Decision-Making [SCDM]):
  • Clinical Rationale: Most sexually active adults have already been exposed to some HPV types; thus, population-wide cost-effectiveness is lower. However, many individuals in this age cohort have not been exposed to all 9 vaccine serotypes.
  • Ideal Candidates: Adults with new sexual partners, multiple partners, or recent relationship dissolution (e.g., divorce), who remain at risk for acquiring new HPV strains.
  • Prophylactic Nature: The vaccine is strictly prophylactic, not therapeutic. It does not treat or accelerate clearance of pre-existing HPV infections, existing anogenital warts, or established cervical dysplasia (CIN).
  • Cervical Cancer Screening Mandate: Emphasize that HPV vaccination does NOT alter cervical cancer screening schedules. Vaccinated women must continue routine cervical cytology and hrHPV cotesting according to USPSTF guidelines.

Dosing Schedules

• Series Initiated Before Age 15 Years (<15th birthday): 2-dose series at 0 and 6–12 months (minimum interval between doses is 5 months; if dose 2 is given <5 months after dose 1, an additional third dose must be given ≥ 12 weeks after dose 2 and ≥ 5 months after dose 1).
• Series Initiated at Age ≥ 15 Years OR Immunocompromised Hosts: 3-dose series at 0, 1–2, and 6 months (minimum intervals: 4 weeks between dose 1 and 2; 12 weeks between dose 2 and 3; 5 months between dose 1 and 3).
• Pregnancy & Lactation: HPV vaccination is deferred during pregnancy. If a woman is discovered to be pregnant after initiating the series, pause the series; remaining doses are administered postpartum (no need to restart). HPV vaccine can be safely administered to breastfeeding individuals.

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Hepatitis B Immunization: Universal Adult Recommendation & Adjuvanted Formulations

The Landmark 2022 ACIP Universal Recommendation

Prior to 2022, adult hepatitis B immunization relied on risk-based screening. Because risk-based strategies failed to increase adult vaccine coverage and required disclosure of stigmatized behaviors (substance use, sexual practices), the ACIP fundamentally restructured the adult schedule:

• Universal Adult Recommendation (Ages 19–59 Years): All adults aged 19 through 59 years should receive hepatitis B vaccination without requiring any disclosure or assessment of risk factors.
• Adults Aged ≥ 60 Years: Recommended for any adult aged ≥ 60 with risk factors, OR any adult aged ≥ 60 without identified risk factors who requests protection against hepatitis B.
• Risk Factors in Older Adults (≥ 60): Chronic liver disease (cirrhosis, NAFLD/MASH, hepatitis C, autoimmune hepatitis), end-stage renal disease (hemodialysis), diabetes mellitus, HIV infection, injection drug use, sexual exposure risk (multiple partners, MSM, history of STIs), healthcare personnel, public safety workers exposed to blood, incarcerated individuals, and travel to regions with high/intermediate HBV endemicity (HBsAg ≥ 2%).

Adult Vaccine Formulations & Regimens

Post-Vaccination Serologic Testing

• Target Population for Serology: Post-vaccination testing is NOT recommended for routine healthy adults. It is strictly indicated for high-risk cohorts:
  1. Healthcare personnel and public safety workers with risk of blood exposure
  2. Hemodialysis patients
  3. Immunocompromised individuals (HIV, chemotherapy, organ transplant)
  4. Sexual partners of HBsAg-positive individuals
• Timing: Serum quantitative anti-HBs (hepatitis B surface antibody) drawn 1 to 2 months after the final dose of the vaccine series.
• Seroprotection Threshold: An anti-HBs titer ≥ 10 mIU/mL defines seroprotection and indicates durable, lifelong immunity against acute and chronic hepatitis B, even if circulating titers subsequently wane below 10 mIU/mL due to immunologic memory.

Management of Non-Responders (anti-HBs < 10 mIU/mL)

1. Step 1 (Repeat Full Series): Administer a second complete vaccine series. (Using the 2-dose Heplisav-B series is highly effective, inducing seroconversion in >80% of prior non-responders to alum-adjuvanted vaccines).
2. Step 2 (Retest): Retest anti-HBs 1 to 2 months after the final dose of the second series.
3. Step 3 (Evaluate for Occult/Chronic Infection): If anti-HBs remains < 10 mIU/mL after two full series (6 total doses of standard vaccine or 2 complete series), test for active or chronic HBV infection by ordering HBsAg and total anti-HBc.
4. Step 4 (Counseling Persistent Non-Responders): If seronegative for HBsAg and anti-HBc, the patient is declared a persistent "non-responder". The patient must be counseled that they remain fully susceptible to HBV. In the event of a documented percutaneous or mucosal exposure to HBsAg-positive blood, they must receive Hepatitis B Immune Globulin (HBIG) immediately (within 24 hours), followed by a second dose of HBIG 1 month later.