How do side effects of Janssen vaccine compare to Pfizer and Moderna?
Executive summary
Clinical reporting and public-health summaries show that common short-term side effects (injection-site pain, fatigue, headache, muscle aches, fever) occur with Pfizer, Moderna and Janssen, but patterns differ: mRNA vaccines (Pfizer, Moderna) tend to cause more frequent local and systemic reactogenicity, while Janssen has been linked to very rare but serious clotting events (thrombosis with thrombocytopenia) not seen with mRNA shots; some analyses also found lower antibody levels and lower initial effectiveness after Janssen versus the mRNA vaccines (e.g., 71% vs. 88–93% against hospitalization in one study) [1] [2] [3] [4]. Coverage across sources is uneven on exact incidence rates and on newer 2024–25 formulary updates; available sources do not mention later booster-era reactogenicity comparisons in detail.
1. What common side effects look like — similar short-term reactions
All three vaccines commonly cause injection-site pain, fatigue, headache, muscle and joint pain, and fever; a cross-sectional study and provider guides list injection-site pain as the top complaint and fatigue/headache among the most frequent systemic reactions for Pfizer and Moderna, and similar short-term complaints appear with Janssen as well [1] [5]. Health-system and consumer sites emphasize that these short-term effects are expected immune responses rather than signs of long-term harm [5].
2. mRNA shots (Pfizer/Moderna): more frequent reactogenicity but no TTS signal
Multiple sources report that the two-dose mRNA vaccines—Pfizer (Comirnaty) and Moderna (Spikevax)—produce robust local and systemic reactions after doses and boosters; some real-world studies and reviews found Moderna produces slightly stronger immune responses and possibly more frequent or intense short-term side effects compared with Pfizer [6] [7]. The European regulator and clinical summaries note lymph node swelling under the arm is a common mRNA-associated effect [2].
3. Janssen (Johnson & Johnson): often milder short-term effects but rare serious clotting
Some earlier FDA reporting and secondary coverage described Janssen’s immediate side effects as “milder and shorter” than the mRNA shots, though reporting varies by study and population [8]. Crucially, regulators identified a rare but serious risk of thrombosis with thrombocytopenia syndrome (TTS) after Janssen vaccination, prompting public-health guidance favoring mRNA vaccines in many settings [2] [9]. The EMA characterized some Janssen-associated events as “very rare,” and U.S. public-health agencies advised use of Pfizer/Moderna over Janssen because of the clotting signal and comparatively lower effectiveness [2] [9].
4. How side effects relate to effectiveness and antibody responses
Comparative effectiveness research showed higher vaccine effectiveness against hospitalization for the mRNA vaccines than for Janssen during early 2021 surveillance: Moderna ~93%, Pfizer ~88%, Janssen ~71% (March–Aug 2021 study). That study also reported significantly lower anti-spike and anti-RBD IgG levels after Janssen than after Pfizer or Moderna, linking lower antibody measures to lower effectiveness in that analysis [3] [4]. Side-effect frequency does not directly predict long-term protection, but the sources show a consistent pairing of stronger antibody responses and higher observed effectiveness for the mRNA products in those datasets [4].
5. Regulators’ reactions and public-health guidance
Because of the TTS signal and evolving data on relative effectiveness, some state and federal public-health bodies recommended Pfizer or Moderna over Janssen; for example, South Carolina’s health department explicitly supported CDC guidance favoring mRNA vaccines citing higher efficacy and the rare blood-clotting risk tied to Janssen [9]. The EMA also updated product information to add rare side effects for Janssen and Moderna, reflecting ongoing pharmacovigilance [2].
6. Limits, disagreements and what sources don’t say
Sources differ on descriptions of immediate reactogenicity: an FDA-summary-style claim that Janssen side effects were “milder and shorter” [8] contrasts with studies finding Pfizer had fewer adverse effects than Moderna in some populations [1]. Incidence rates for common short-term reactions vary by study design and population; precise, current incidence numbers for boosters or newer variant-targeted formulations are not covered in these documents. Available sources do not mention head-to-head randomized trials of current booster formulas or up-to-date reactogenicity comparisons for 2024–25 vaccine editions [7] [10].
7. What this means for individuals deciding between vaccines
If the key concern is avoiding rare clotting events, the mRNA vaccines are favored in the cited public-health guidance because TTS was associated with Janssen [2] [9]. If reactogenicity (short-lived soreness, fever, malaise) is the priority, some sources report Janssen’s immediate side effects may be less intense or shorter-lived, but this is not universally observed and must be weighed against Janssen’s lower antibody levels and lower observed effectiveness in some studies [8] [3] [4].
Sources cited: [1], [5], [6], [7], [2], [3], [4], [9], [8], [10].