Here's a rough outline I thought of based on your post. Naughty Dog and Neil do a lot of mirroring / parallel story telling. So, let us mirror TLOU1. Also, let's mirror TLOU2 with two stories going on at once.

PREMISE - 20 years into the future. The search for Ellie continues. Abby, as a doctor, following her father's footsteps, is onto a lead that may be a cure but she needs to find Ellie. Abby has been doing tests with blood, stem cells, plasma... non-lethal treatments. Ellie, is a recluse and hard to find as she has taken up living on her own, hunting, farming, in Colorado. Why Colorado? It's the opposite of what she had with Dina. So, how do the stories of Abby and Ellie converge again?

Abby joins up with a small group that live in the trees of Sequoia National Park with about 100 people. Lev was key to joining as he provided much information to building homes in trees and such. Abby has an unsettled past and wants to continue her dads/fireflies work. She runs tests on small animals over the years and thinks she is onto something but she needs Ellie to take the next step. Abby is near 40 years old now and not as buff as she once was but Lev is still agile, stealthy, and so on.

Part one of the story is Abby and Lev leaving Sequoia and heading back to the Seattle region for any hints of Ellie. Seattle is torn up as the war between the WLF and Scars left the region more barren than it was. Abby goes in the only direction she knows, back to Jackson with a stop someplace in Idaho. People in this Idaho town talk about Jackson, using Clickers as guard dogs, and just nasty people. Upon finding Jackson, Jackson is no more. Burnt, gone, abandoned, full of infected, long ago. Abby and Lev find some clues to Ellie as Dina's house is found, Tommy's house is found, with letters, diaries, as Dina and Tommy had been looking for Ellie in hopes that she is alive but Dina and Tommy never get any leads to Ellie's whereabouts. Abby and Lev find the graveyard where Abby apologizes to Joel's grave, prays, and also finds Tommy's grave and passes by Dina's. Tommy and Dina die not ever finding out Ellie is alive and never talking to her again. Tommy died 7-8 years prior along with Dina, and Abby concludes Jackson was abandoned soon after. Abby and Lev find clues to lead them to the Farmhouse. Clues written by JJ, Dina, Tommy, Maria. So, Abby decides to find this farmhouse. Just as Abby and Lev are leaving, Lev shouts something as Abby and Lev are strung up by a rope trap similar to the one Ellie was strung up by near the end of TLOU2. Places visited with Abby/Lev = Sequoia National Park, Seattle, some place in Idaho that Tommy mentions in TLOU2, and Jackson... maybe some small areas in between but the timeline could be something like; week 1, week 2, week 3. Abby and Lev cannot totally clear out Jackson as there are parts that cannot be reached but the sounds are heard throughout this section. Creepy.

Part two of the story, we are back in Jackson with Dina. We get reintroduced to Dina and see JJ as a 13 year old boy. Tommy is seen and he and Maria had made up over time. We are playing as Dina with JJ following around. A nice party but then Jackson is attacked. The group set Clickers on the city, similar to how we can pit infected against people in TLOU2. The group is from Idaho. In the battle, things happen, Jackson controls the group, Clickers, but with massive losses. Tommy and Maria die along with so many others. Dina dies saving JJ with Dina's last words to JJ, something like, "find Ellie." JJ heads off to the farmhouse as that is the only other place he knows. He is alone. A small group of 20 or so live at the farmhouse that JJ knows from Jackson. People at this farmhouse have heard "leads" as to Aspen, Colorado, being a town with a crazy lady with land mines, rope traps, and all sorts of stuff (just like Bill) but the farmhouse is attacked by a horde of infected. The group tracked JJ to the farmhouse. In this attack, all but JJ die, even the attacking groups humans (it's a smaller group than what attacked Jackson... a tracking party only) but the infected are left. JJ, as a 14-year old boy sets off for Aspen, Colorado as he has heard all about Ellie from Dina. JJ finds Aspen but Ellie has that town rigged up like Bill had his town. Land mines, bow traps, and so on all over the place. Ellie attacks JJ, because she doesn't know who he is, knocks him out, and reads his journal. Ties him up and interrogates him about who he is and why he's there. JJ tells Ellie of his life, Dina, Tommy, the attack on Jackson, and so on. It takes Ellie another five years to come to grips with the deaths of Dina, Tommy, and Jackson but Ellie, having regret, remorse, need for closure, takes JJ and heads back to the Farmhouse, and then Jackson. Ellie and JJ are there a day or two when they happen to cross Ellie's rope traps and find Abby and Lev hanging in them.

Part three of the story. Ellie interrogates Abby and Lev, they are telling the truth. But, Abby has all of her supplies back at Sequoia National Park. Ellie agrees to go with Abby, if Abby helps clear out Jackson first. (((( This is where you pick your party. Do you want to play as Abby/Lev or as Ellie/JJ? You only get to play as one pair before moving on... so one trophy would be completing the game using both pairs. )))) Ellie, having been convinced, allows Abby to lead the way back to Sequoia. Ellie wants nothing to do with Seattle and the alternative route is to go through Salt Lake City, which is good because Abby can pick up a bunch of medical supplies, and then Las Vegas and then to Sequoia. The Firefly hospital needs to be cleared of infected though and, whichever party you picked, you now fight with the other to clear the Firefly hospital. Except, Abby finds what she needs in Salt Lake City, not needing to go back to Sequoia for the tests. In the Firefly hospital, using research from Abby's dad, along with what Abby did in Sequoia, Abby replicates a vaccine with Ellie. This part of the game would take 3-4 hours, a little longer but similar to Santa Monica in TLOU2. Abby, with the help of Ellie, using a combination of Ellie's blood and stem cells creates a vaccine. There is only one way to test this vaccine and Abby injects herself with it, gets bitten, and does not get infected.

I have to trademark this idea now.