COVID-19 vaccines have been crucial in protecting against severe disease and death. For that, we’re grateful.
Keep our gratitude in mind when we ask this next question, because we really don’t mean to look a gift horse in the mouth. With several COVID-19 vaccine options available, how can you know which one fits you specifically?
Especially when everybody — and every body — is different.
Understanding the similarities and differences is the first step. Below we’ve laid out the technology, dosing, side effects, and our actual recommendations for the four COVID-19 vaccines available this season.
But before you read further, the thing that matters most: any COVID-19 vaccine beats no vaccine. Everything after this is optimization.
In This Article:
- How COVID-19 vaccines work
- The four options for 2026-2027
- What happened to those 95% efficacy numbers
- Key factors to consider
- What we actually recommend
Understanding How COVID-19 Vaccines Work
Vaccines coach your immune system to recognize and fight a virus. By exposing your immune system to a small, harmless piece of the pathogen, it gets to develop specialized cells for that specific threat. Meet the real thing later, and your body already has a game plan.
Dr. Neal likens vaccines to training camp for your immune system.
The COVID-19 vaccines available today work one of two ways:
mRNA vaccines use messenger RNA — a set of instructions telling your cells to build a piece of the virus’s spike protein, which your immune system then learns to recognize. The mRNA breaks down within days. It cannot cause COVID, and it never enters or alters your DNA. Comirnaty, Spikevax, and mNEXSPIKE all use this approach.
Protein subunits vaccines skip the instruction step and deliver the protein piece directly, alongside an adjuvant that amplifies the immune response. Nuvaxovid uses this approach.
Learn More: Vaccine Ingredients in 2026: Less Scary Than You Might Think
The Four Options for 2026-2027
All four target XFG, the JN.1-descended variant that’s been dominant in the U.S. All were approved on August 27, 2026. All four labels cover adults 65 and older, plus younger people with at least one condition that raises their risk of severe COVID.
Comirnaty (Pfizer-BioNTech)
- Technology: mRNA, encoding the full spike protein
- Ages: 65+; ages 5-64 with a qualifying condition
- Schedule: a single updated dose for most people
Spikevax (Moderna)
- Technology: mRNA, encoding the full spike protein
- Ages: 65+; ages 6 months-64 years with a qualifying condition — the broadest pediatric coverage of the four
- Schedule: a single updated dose for most people
mNEXSPIKE (Moderna)
- Technology: mRNA, but next-generation. Rather than coding for the entire spike protein, it codes only for the two regions most antibodies actually target. That focus lets it work at a much smaller dose — 10 micrograms versus 50 for Spikevax.
- Ages: 65+; ages 12-64 with a qualifying condition
- Schedule: a single updated dose. Note the interval is 3 months since your last COVID vaccine, rather than the 2 months that applies to the others.
Nuvaxovid (Novavax, commercialized by Sanofi)
- Technology: protein subunit with Matrix-M adjuvant — the only non-mRNA option available in the U.S.
- Ages: 65+; ages 12-64 with a qualifying condition
- Schedule: a single updated dose if you’ve been vaccinated before. If you have never received any COVID vaccine, Nuvaxovid is a two-dose series.
What Happened to Those 95% Efficacy Numbers?
If you’ve read an older version of this article — including ours — you saw figures like 95% for Pfizer, 94% for Moderna, 90% for Novavax. We’ve removed them, and you should know why.
Those numbers came from the original 2020 trials. They measured the original two-dose primary series against the original ancestral strain, in a population with essentially no prior immunity. Every one of those conditions is gone. Almost everyone now has immunity from vaccination, infection, or both, and the virus has changed enormously.
Quoting those figures today isn’t just outdated — it sets an expectation the current vaccines were never designed to meet, and then makes them look like failures when they don’t prevent every sniffle.
Here’s the honest current picture. Updated annual COVID vaccines are evaluated primarily on immune response and real-world effectiveness against serious outcomes. Interim data from the 2025-2026 season showed protection against COVID-related emergency department visits and hospitalizations in both immunocompromised and non-immunocompromised patients.
They reduce your chance of getting infected somewhat, for a few months. They reduce your chance of a bad outcome substantially, for longer. That second thing is the point. It always was.
Learn More: Vaccines Do Work, But They’re Not Perfect
Key Factors to Consider
Age and Risk Status
This is the big one, and it determines eligibility as much as preference. If you’re 65 or older, all four are on the table. If you’re under 65, the labels require at least one qualifying condition — and that list is long, including obesity, diabetes, asthma, heart disease, kidney disease, and pregnancy. Most people who wonder whether they qualify do. Ask us.
For children, Spikevax has the widest approval, down to 6 months.
Side Effects
All vaccines produce some side effects. We like to think of them as tangible evidence your immune system is running the drill.
The most common are injection site pain, fatigue, headache, muscle aches, and sometimes a low fever. These are generally mild and resolve within a day or two.
Some real differences worth knowing:
- Spikevax tends to produce the most noticeable reactions of the group, particularly arm soreness. Higher dose, bigger response, more of a next-day.
- mNEXSPIKE showed a safety profile generally similar to Spikevax in trials, at one-fifth the mRNA dose.
- Nuvaxovid is often reported as gentler, more in line with the side effect profile people expect from a flu shot.
Storage — Much Less Relevant Than It Used To Be
Early in the pandemic, ultra-cold storage requirements genuinely limited where you could get a Pfizer shot. That era is over. All four products now handle standard refrigeration for meaningful periods, and mNEXSPIKE moved to refrigerated storage for 2026-2027 with no thawing step at all.
We mention it only because older articles still make a big deal of it. For you as a patient, it no longer affects anything.
So What Do We Actually Recommend?
We used to end this article by saying we wouldn’t pick one for you. That was a bit of a cop-out. Here’s a straighter answer.
Our default is Moderna, and for patients 65+ or at high risk, mNEXSPIKE specifically. The more focused antigen design at a lower dose is elegant, storage is simpler, and in Moderna’s trial it showed numerically higher relative efficacy compared to Spikevax. We’ll be honest about the size of that last claim: the study wasn’t designed to prove superiority, so “numerically higher” is what it is, not proof of a better vaccine.
If you don’t want an mRNA vaccine, take Nuvaxovid. We mean that without any eye-rolling. It’s a genuinely good vaccine using well-established protein subunit technology, and it’s a real option rather than a consolation prize. It’s also our suggestion if you’ve had rough reactions to mRNA doses before and that’s what’s keeping you from getting boosted.
If you’ve had Comirnaty every year and it’s been fine, keep having Comirnaty. The differences between these products are small compared to the difference between being vaccinated and not. Continuity has value, especially if it means you’ll actually show up.
And never skip a dose waiting for a specific brand. If we have one and not another, take the one we have. A vaccine in your arm in September beats your preferred brand in December.
If you want to talk it through, that’s what we’re here for.
What About Boosters?
Quick terminology update: we mostly don’t say “booster” anymore, because it isn’t quite what’s happening.
A booster implies topping up the same formula. What you’re getting now is an updated vaccine — reformulated annually to match circulating variants, the way flu vaccine is. This year’s targets XFG, which last year’s didn’t.
So even if you’re fully caught up on previous doses, this season’s vaccine is a different product aimed at a different target.
Who needs what:
- Most people: one updated dose per year.
- Adults 65+ and moderately-to-severely immunocompromised patients: generally eligible for a second dose about 6 months after the first.
- Wait at least 2 months after your most recent COVID vaccine — 3 months for mNEXSPIKE.
- If you’ve recently had COVID, you have some natural protection. We generally suggest waiting a couple of months after recovery.
Timing this year: the vaccines arrived late August and there’s already meaningful COVID activity. Unlike flu, where we tell you to wait for October, the advice on COVID is to come in now.
Learn More: Dr. Neal’s Vaccine Recommendations Rundown: Who Needs What and When
Making an Informed Decision After Comparing COVID Vaccines
Making an Informed Decision
Here’s the recap if you scrolled to the bottom:
- Four options this year, all targeting XFG: Comirnaty, Spikevax, mNEXSPIKE, and Nuvaxovid.
- Nuvaxovid is the only non-mRNA choice, and a legitimate one.
- The old 95% efficacy figures don’t apply to today’s vaccines or today’s virus. Judge these on protection against hospitalization, which is what they’re built for.
- We lean Moderna, and mNEXSPIKE for older and higher-risk patients — while cheerfully admitting the gaps between products are modest.
- The gap that isn’t modest is between vaccinated and unvaccinated.
We know everyone is tired of hearing about COVID. It appears to be sticking around anyway, and the people it sends to the hospital are still disproportionately older adults and people with chronic conditions.
If you have questions we didn’t address, give us a call. Because Village Apothecary is decidedly not a big-box pharmacy, our vaccination experts — who are humans, not chatbots — are ready to answer them and simplify this for you, specifically.